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Gallego-Barceló P, Benítez-Álvarez D, Bagues A, Silván-Ros B, Montalbán-Rodríguez A, López-Gómez L, Vera G, del Castillo MD, Uranga JA, Abalo R. Ex Vivo Study of Colon Health, Contractility and Innervation in Male and Female Rats after Regular Exposure to Instant Cascara Beverage. Foods 2024; 13:2474. [PMID: 39200401 PMCID: PMC11353626 DOI: 10.3390/foods13162474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 07/31/2024] [Accepted: 08/01/2024] [Indexed: 09/02/2024] Open
Abstract
Instant Cascara (IC) is a sustainable beverage made from dried coffee cherry pulp, a by-product of coffee processing. It is rich in nutrients and bioactive compounds and has a high concentration of antioxidants. This study explored the impact of regular IC consumption on colonic motor function and innervation. Over a period of 4 weeks, male and female healthy rats were given drinking water containing 10 mg/mL of IC. Thereafter, colon samples were obtained to evaluate the longitudinal (LM) and circular (CM) smooth muscle contractile response to acetylcholine (ACh) and electrical field stimulation (EFS) in an organ bath, before and after atropine administration (10-6 M). Histological and immunohistochemical analyses assessed colon damage, muscle thickness, and immunoreactivity to substance P (SP) and neuronal nitric oxide synthase (nNOS). ACh and EFS induced similar responses across groups, but the CM response to EFS was greater in females compared with males, despite their lower body weight. Atropine completely blocked the response to ACh but only partially antagonized the neural response to EFS, particularly that of CM in females treated with IC, which had a greater liquid intake than those exposed to water. However, in the myenteric ganglia, no statistically significant differences were observed in SP or nNOS. Our results suggest that regular IC exposure may enhance specific neural pathway functions, particularly in females, possibly due to their increased IC consumption.
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Affiliation(s)
- Paula Gallego-Barceló
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (P.G.-B.); (D.B.-Á.); (B.S.-R.); (A.M.-R.); (L.L.-G.); (G.V.); (J.A.U.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
| | - David Benítez-Álvarez
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (P.G.-B.); (D.B.-Á.); (B.S.-R.); (A.M.-R.); (L.L.-G.); (G.V.); (J.A.U.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
- Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Street 34, 50931 Cologne, Germany
- Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Street 21, 50931 Cologne, Germany
| | - Ana Bagues
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (P.G.-B.); (D.B.-Á.); (B.S.-R.); (A.M.-R.); (L.L.-G.); (G.V.); (J.A.U.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
- High Performance Research Group in Experimental Pharmacology (PHARMAKOM-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain
- Associated I+D+i Unit to the Institute of Medicinal Chemistry (IQM), Scientific Research Superior Council (CSIC), 28006 Madrid, Spain
| | - Blanca Silván-Ros
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (P.G.-B.); (D.B.-Á.); (B.S.-R.); (A.M.-R.); (L.L.-G.); (G.V.); (J.A.U.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
- Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland
| | - Alba Montalbán-Rodríguez
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (P.G.-B.); (D.B.-Á.); (B.S.-R.); (A.M.-R.); (L.L.-G.); (G.V.); (J.A.U.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
| | - Laura López-Gómez
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (P.G.-B.); (D.B.-Á.); (B.S.-R.); (A.M.-R.); (L.L.-G.); (G.V.); (J.A.U.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
| | - Gema Vera
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (P.G.-B.); (D.B.-Á.); (B.S.-R.); (A.M.-R.); (L.L.-G.); (G.V.); (J.A.U.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
- Associated I+D+i Unit to the Institute of Medicinal Chemistry (IQM), Scientific Research Superior Council (CSIC), 28006 Madrid, Spain
| | - María Dolores del Castillo
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
- Food Bioscience Group, Department of Bioactivity and Food Analysis, Institute of Food Science Research (CIAL) (CSIC-UAM), Nicolás Cabrera Street, 9, 28049 Madrid, Spain
| | - José A. Uranga
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (P.G.-B.); (D.B.-Á.); (B.S.-R.); (A.M.-R.); (L.L.-G.); (G.V.); (J.A.U.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
| | - Raquel Abalo
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (P.G.-B.); (D.B.-Á.); (B.S.-R.); (A.M.-R.); (L.L.-G.); (G.V.); (J.A.U.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain; (M.D.d.C.)
- Associated I+D+i Unit to the Institute of Medicinal Chemistry (IQM), Scientific Research Superior Council (CSIC), 28006 Madrid, Spain
- Working Group of Basic Sciences on Pain and Analgesia of the Spanish Pain Society, 28046 Madrid, Spain
- Working Group of Basic Sciences on Cannabinoids of the Spanish Pain Society, 28046 Madrid, Spain
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López-Tofiño Y, Barragán del Caz LF, Benítez-Álvarez D, Molero-Mateo P, Nurgali K, Vera G, Bagües A, Abalo R. Contractility of isolated colonic smooth muscle strips from rats treated with cancer chemotherapy: differential effects of cisplatin and vincristine. Front Neurosci 2023; 17:1304609. [PMID: 38192512 PMCID: PMC10773793 DOI: 10.3389/fnins.2023.1304609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 11/27/2023] [Indexed: 01/10/2024] Open
Abstract
Background Certain antineoplastic drugs cause gastrointestinal disorders even after the end of treatment. Enteric neuropathy has been associated with some of these alterations. Our goal was to assess the impact of repeated treatment with cisplatin and vincristine on the contractility of circular and longitudinal muscle strips isolated from the rat colon. Methods Two cohorts of male rats were used: in cohort 1, rats received one intraperitoneal (ip) injection of saline or cisplatin (2 mg kg-1 week-1) on the first day of weeks 1-5; in cohort 2, rats received two cycles of five daily ip injections (Monday to Friday, weeks 1-2) of saline or vincristine (0.1 mg kg-1 day-1). Body weight and food and water intake were monitored throughout the study. One week after treatment, responses of colonic smooth muscle strips to acetylcholine (10-9-10-5 M) and electrical field stimulation (EFS, 0.1-20 Hz), before and after atropine (10-6 M), were evaluated in an organ bath. Results Both drugs decreased body weight gain. Compared to saline, cisplatin significantly decreased responses of both longitudinal and circular smooth muscle strips to EFS, whereas vincristine tended to increase them, although in a non-significant manner. No differences were observed in the muscle response to acetylcholine. Atropine abolished the contractile responses induced by acetylcholine, although those induced by EFS were only partially reduced in the presence of atropine. Conclusion The findings suggest that although both drugs cause the development of enteric neuropathy, this seems to have a functional impact only in cisplatin-treated animals. Understanding the effects of chemotherapy on gastrointestinal motor function is vital for enhancing the quality of life of cancer patients.
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Affiliation(s)
- Yolanda López-Tofiño
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), Alcorcón, Spain
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut), University Rey Juan Carlos (URJC), Alcorcón, Spain
- International Doctoral School, URJC, Móstoles, Spain
| | | | - David Benítez-Álvarez
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), Alcorcón, Spain
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut), University Rey Juan Carlos (URJC), Alcorcón, Spain
| | - Paula Molero-Mateo
- International Doctoral School, URJC, Móstoles, Spain
- Lescer Center (Neurological Rehabilitation), Madrid, Spain
- Department of Physiotherapy, Occupational Therapy, Rehabilitation and Physical Medicine, URJC, Alcorcón, Spain
| | - Kulmira Nurgali
- Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
- Department of Medicine Western Health, The University of Melbourne, Melbourne, VIC, Australia
- Regenerative Medicine and Stem Cell Program, Australian Institute for Musculoskeletal Science (AIMSS), Melbourne, VIC, Australia
| | - Gema Vera
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), Alcorcón, Spain
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut), University Rey Juan Carlos (URJC), Alcorcón, Spain
- Associated I+D+i Unit to the Institute of Medicinal Chemistry (IQM), Scientific Research Superior Council (CSIC), Madrid, Spain
| | - Ana Bagües
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), Alcorcón, Spain
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut), University Rey Juan Carlos (URJC), Alcorcón, Spain
- Associated I+D+i Unit to the Institute of Medicinal Chemistry (IQM), Scientific Research Superior Council (CSIC), Madrid, Spain
- High Performance Research Group in Experimental Pharmacology (PHARMAKOM-URJC), URJC, Alcorcón, Spain
| | - Raquel Abalo
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), Alcorcón, Spain
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut), University Rey Juan Carlos (URJC), Alcorcón, Spain
- Associated I+D+i Unit to the Institute of Medicinal Chemistry (IQM), Scientific Research Superior Council (CSIC), Madrid, Spain
- Working Group of Basic Sciences on Pain and Analgesia of the Spanish Pain Society, Madrid, Spain
- Working Group of Basic Sciences on Cannabinoids of the Spanish Pain Society, Madrid, Spain
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Yao H, Fu X, Xu Q, Li T, Li Y, Kang Y, Wu Q. The macrophages regulate intestinal motility dysfunction through the PGE2 Ptger3 axis during Klebsiella pneumonia sepsis. Front Immunol 2023; 14:1147674. [PMID: 37063880 PMCID: PMC10090685 DOI: 10.3389/fimmu.2023.1147674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 03/16/2023] [Indexed: 03/31/2023] Open
Abstract
IntroductionGut motility dysfunction, the most common complication of post-septic organ dysfunction, depends on immune and neuronal cells. This study aimed to investigate the mechanisms that activate these cells and the contribution of macrophages to the recovery of intestinal motility dysfunction after sepsis.Materials and methodsPostoperative gut motility dysfunction was induced by establishing Klebsiella pneumonia sepsis in mice with selective deletion of neutrophils and macrophages in the gut. The distribution of orally administered fluorescein isothiocyanate-dextran and carmine excretion time was used to determine the severity of small bowel disease. The effect of macrophages on intestinal motility was evaluated after prostaglandin E2 therapy.ResultsWe found that muscular neutrophil infiltration leading to neuronal loss in the intestine muscle triggered intestinal motility dysfunction after pneumonia sepsis; however, reduced neutrophil infiltration did not improve intestinal motility dysfunction. Moreover, macrophage depletion aggravated gut motility dysfunction. The addition of macrophages directly to a smooth muscle was responsible for the recovery of intestinal motility.ConclusionOur results suggest that a direct interaction between macrophages and smooth muscle is neurologically independent of the restoration of intestinal dysmotility.
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Affiliation(s)
| | | | | | | | | | - Yan Kang
- *Correspondence: Yan Kang, ; Qin Wu,
| | - Qin Wu
- *Correspondence: Yan Kang, ; Qin Wu,
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The sources of calcium for noradrenaline-induced contraction in the human thoracic internal artery. Pflugers Arch 2017; 469:1135-1140. [PMID: 28434061 DOI: 10.1007/s00424-017-1982-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 03/26/2017] [Accepted: 04/11/2017] [Indexed: 10/19/2022]
Abstract
The aim of the present study was to examine the contribution of intracellular and extracellular calcium sources in contraction caused by noradrenaline (NA) of the human internal thoracic artery (ITA) in vitro. Distal segments of ITA were obtained from 20 patients (aged 38-73, at the time of routine coronary artery surgical revascularization (CABG)). Contractile responses to 10-6 mol/L NA in the physiological salt solution and in Ca2+-free solution without and after incubation with 10-6 mol/L thapsigargin (TSG) were recorded under isometric conditions. Responses of ITA rings to 1 μM NA without incubation with TSG accounted (% of reaction to 80 mM KCl) 224.70 ± 14.06% in PSS solution, 141.30 ± 8.66% in Ca2+-free solution, and 80.03 ± 1.71% after PSS restoration and were statistically significantly different (p < 0.0001, one-way ANOVA). Responses of ITA rings to 1 μM NA with 1 μM TSG accounted (% of reaction to 80 mM KCl) 114.50 ± 2.79% in Ca2+-free solution and 36.70 ± 2.38% after PSS restoration. Responses in Ca2+-free solution and after PSS restoration without and with TSG were statistically significantly different (p = 0.0257 and p < 0.0001, respectively-t test). ITA contraction is caused by calcium derived not only from the SR and the extracellular matrix. The delivery of calcium to the space surrounding tissue does not immediately deliver calcium to the myofilaments.
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Patejdl R, Leroux AC, Noack T. Phenytoin inhibits contractions of rat gastrointestinal and portal vein smooth muscle by inhibiting calcium entry. Neurogastroenterol Motil 2015; 27:1453-65. [PMID: 26265316 DOI: 10.1111/nmo.12645] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Accepted: 07/07/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Phenytoin is widely used as a second-line treatment for status epilepticus. Besides its well-known cardiac pro-arrhythmogenicity, side effects on other organ systems have received less attention. METHODS This study investigates the effects of phenytoin on gastrointestinal tissue function using an in vitro model of smooth muscle preparations from rats by combining registrations of pharmacological effects on mechanical contractions, electric field potentials, and dynamic intravital fluorescence microscopy. KEY RESULTS When added to the bathing solution at a concentration of 30 μM, phenytoin reduced the frequency of spontaneous activity significantly in antrum and portal vein preparations to 72.2 ± 36.5% (p = 0.022) and 80.7 ± 24.4% (p = 0.037) of control values, respectively. At a concentration of 100 μM, the height of spontaneous contractions declined to 9.8 ± 19.6% (p = 0.005) (antrum), 15.7 ± 28.2% (p = 0.004) (portal vein), and 31.8 ± 31.3% (p = 0.005) (colon) in comparison to the control conditions before the application of phenytoin. Depolarization triggered increases in calcium dependent fluorescence signals were reduced by 52.8 ± 39.1% (p = 0.012) The inhibition of spontaneous activity caused by phenytoin was reduced in the presence of the L-type calcium channel agonist BAY K8644(-). CONCLUSIONS & INFERENCES Phenytoin exerts strong inhibitory effects on the spontaneous and stimulated contractile activity of smooth muscles from both the upper and lower gastrointestinal tract. The mechanism underlying this effect is not related to the sodium channel blocking activity of phenytoin, but is rather caused by an inhibition of calcium entry through voltage dependent L-type calcium channels. The results of this study should raise vigilance to gastrointestinal complications in patients treated with phenytoin.
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Affiliation(s)
- R Patejdl
- Institut für Physiologie, Universitätsmedizin Rostock, Rostock, Germany
| | - A-C Leroux
- Institut für Physiologie, Universitätsmedizin Rostock, Rostock, Germany
| | - T Noack
- Institut für Physiologie, Universitätsmedizin Rostock, Rostock, Germany
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Wei YY, Sun LL, Fu ST. HEF-19-induced relaxation of colonic smooth muscles and the underlying mechanisms. World J Gastroenterol 2013; 19:5314-5319. [PMID: 23983435 PMCID: PMC3752566 DOI: 10.3748/wjg.v19.i32.5314] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Accepted: 07/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relaxant effect of chromane HEF-19 on colonic smooth muscles isolated from rabbits, and the underlying mechanisms.
METHODS: The relaxant effect and action mechanisms of HEF-19 were investigated using descending colon smooth muscle of the rabbits. Preparations 1 cm long were mounted in 15-mL tissue baths containing Tyrode’s solution, maintained at 37 ± 0.5 °C and aerated with a mixture of 5% CO2 in oxygen (Carbogen). The tension and amplitude of the smooth muscle strips were recorded after adding HEF-19 (10-6, 10-5 and 10-4 mol/L). After cumulative administration of four antispasmodic agents, including acetylcholine chloride (Ach) (10-4 mol/L), histamine (10-4 mol/L), high-K+ (60 mmol/L) and BaCl2 (8.2 mmol/L), HEF-19 (3 × 10-7-3 × 10-4 mol/L) was added to investigate the relaxant effect of HEF-19. CaCl2 (10-4-2.5 × 10-3 mol/L) was added cumulatively to the smooth muscle preparations pretreated with and without HEF-19 (1 × 10-6 or 3 × 10-6 mol/L) and verapamil (1 × 10-7 mol/L) to study the mechanisms involved. Finally, phasic contraction was induced with ACh (15 × 10-6 mol/L), and CaCl2 (4 × 10-3 mol/L) was added to the smooth muscle preparations pretreated with and without HEF-19 (3 × 10-6 mol/L or 1 × 10-5 mol/L) and verapamil (1 × 10-7 mol/L) in calcium-free medium to further study the underlying mechanisms.
RESULTS: HEF-19 (1 × 10-6, 1 × 10-5 and 1 × 10-4 mol/L) suppressed spontaneous contraction of rabbit colonic smooth muscles. HEF-19 (3 × 10-7-3 × 10-4 mol/L) relaxed in a concentration-dependent manner colonic smooth muscle preparations pre-contracted with BaCl2, high-K+ solution, Ach or histamine with respective EC50 values of 5.15 ± 0.05, 5.12 ± 0.08, 5.58 ± 0.16 and 5.25 ± 0.24, thus showing a spasmolytic activity. HEF-19 (1 × 10-6 mol/L and 3 × 10-6 mol/L) shifted the concentration-response curves of CaCl2 to the right and depressed the maximum response to CaCl2. The two components contracted by Ach were attenuated with HEF-19 (3 × 10-6 mol/L or 10-5 mol/L) in calcium-free medium.
CONCLUSION: HEF-19 inhibited rabbit colonic smooth muscle contraction, probably through inhibiting opening of voltage-dependent Ca2+ channels. HEF-19 reduced inflow and intracellular release of Ca2+ ions.
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Ragy M, Elbassuoni E. The role of nitric oxide and L-type calcium channel blocker in the contractility of rabbit ileum in vitro. J Physiol Biochem 2012; 68:521-8. [PMID: 22528554 DOI: 10.1007/s13105-012-0167-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2011] [Accepted: 03/30/2012] [Indexed: 01/30/2023]
Abstract
Nitric oxide (NO) and calcium channel blockers are two agents that can affect gastrointestinal motility. The goal of this work was to study the rabbit intestinal smooth muscle contraction response to (1) sodium nitroprusside (SNP), the NO donor, and its potential mechanism of action, and (2) nifedipine, the L-type Ca(2+) channel blocker; to clarify the degree of participation by extra- and intracellular Ca(2+) in smooth muscle contraction. We used standard isometric tension and intracellular micro-electrode recordings. To record the activity of the longitudinal smooth muscle of the ileum, segments of 1.5 cm length of the ileum were suspended vertically in organ baths of Krebs solution. The mechanical activity of the isolated ileal longitudinal muscle was recorded. Different substances were added, and the changes produced on spontaneous contraction were recorded. We found that SNP produced significant decrease, while nitric oxide synthase inhibitor produced significant increase in the amplitude of spontaneous contractions. Both apamin, the Ca(2+)-dependent K(+) channel blocker, and methylene blue, the inhibitor of soluble guanylate cyclase, alone, partially decreased relaxation induced by SNP. Addition of both methylene blue and apamine together abolished the inhibitory effect produced by SNP on spontaneous contractions. Nifedipine produced significant decrease in the amplitude of spontaneous contractions. In conclusion, in longitudinal muscle of rabbit ileum, calcium channels blocker are potent inhibitors of spontaneous activity. However, both extracellular and intracellular Ca(2+) participates in the spontaneous contractions. NO also has inhibitory effect on spontaneous activity, and this effect is mediated by cGMP generation system and Ca(2+)-dependent K(+) channels.
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Affiliation(s)
- Merhan Ragy
- Faculty of Medicine, Department of Physiology, Minia University, 61111, Minia, Egypt
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Aguiar LA, Porto RS, Lahlou S, Ceccatto VM, Barbosa R, Lemos TLG, dos Santos HS, Coelho-de-Souza AN, Magalhães PJC, Zin WA, Leal-Cardoso JH. Antispasmodic effects of a new kaurene diterpene isolated from Croton argyrophylloides on rat airway smooth muscle. ACTA ACUST UNITED AC 2012; 64:1155-64. [PMID: 22775219 DOI: 10.1111/j.2042-7158.2012.01494.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
OBJECTIVES The effects of rel-(1S,4aS,7S,8aS)-7-(1-vinyl)-tetradecahydro-1,4a-dimethylphenanthrene-7,8a-carbolactone-1-carboxylic acid (TCCA), a new ent-kaurene diterpene isolated from Croton argyrophylloides, on rat tracheal preparations were investigated. METHODS Tracheae were removed and cut into two-cartilage segments that were mounted in organ baths containing Tyrode's solution. RESULTS TCCA reduced the contractions induced by electrical field stimulation, relaxed K(+)-induced contractions, and inhibited both phasic and tonic components of the K(+)- and ACh-induced contractions. TCCA reduced the serotonin-induced contraction, abolished that evoked by K(+) in the presence of epinephrine, and also reduced the ACh-induced contractions under Ca(2+)-free conditions. TCCA blocked contractions that depend on divalent cation inflow through voltage-operated Ca(2+) channels (VOCCs) and receptor-operated Ca(2+) channels (ROCCs), but had greater potency to block VOCC- than ROCC-dependent contractions or contractions induced by ACh in Ca(2+)-free conditions. TCCA relaxed the phorbol 12,13 dibutyrate (1 µm) induced contraction, but with slight potency. CONCLUSIONS TCCA induces an antispasmodic effect through several mechanisms including blockade of either VOCCs (with greater potency) or ROCCs, blockade of IP(3)-induced Ca(2+) release from sarcoplasmic reticulum (with intermediate potency) and reduction of the sensitivity of contractile proteins to Ca(2+).
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Affiliation(s)
- Liza Araújo Aguiar
- Electrophysiology Laboratory, Superior Institute of Biomedical Sciences, State University of Ceará, Fortaleza, Brazil
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Evans ED, Mangel AW. Depolarization-stimulated contractility of gastrointestinal smooth muscle in calcium-free solution: a review. ISRN GASTROENTEROLOGY 2010; 2011:692528. [PMID: 21991526 PMCID: PMC3168483 DOI: 10.5402/2011/692528] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2010] [Accepted: 11/03/2010] [Indexed: 12/02/2022]
Abstract
The membrane of most gastrointestinal smooth muscles shows slow waves, slow rhythmic changes in membrane potential. Slow waves serve to bring the membrane potential of smooth muscle cells to a threshold level that elicits a second electrical event known as the spike or action potential. The inward current of the spike, in most gastrointestinal smooth muscle preparations, is carried, at least in part, by calcium. Indeed, considering the narrow diameter of smooth muscle cells, some have hypothesized that the influx of calcium during the spike is sufficient for activation of the contractile machinery. Findings consistent with this include marked reduction in contractility during exposure of muscle segments to blockers of L-type calcium channels or following reductions in external calcium levels. However, it has also been observed that following exposure of muscle segments to external bathing solutions containing no added calcium plus 5 mM EGTA to remove any remaining extracellular calcium, contractions can be triggered following membrane depolarization. It is noteworthy that in isolated smooth muscle cells or in small muscle segments, during incubation in calcium-free solution, depolarization does not induce contractions. The present paper discusses the evidence in support of depolarization-mediated contractions occurring in gastrointestinal smooth muscle segments during incubation in solutions devoid of calcium.
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Affiliation(s)
- Emily D Evans
- RTI-Health Solutions, 3040 Cornwallis Drive, Research Triangle Park, NC 27709, USA
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Lima FC, Peixoto-Neves D, Gomes MDM, Coelho-de-Souza AN, Lima CC, Araújo Zin W, Magalhães PJC, Saad L, Leal-Cardoso JH. Antispasmodic effects of eugenol on rat airway smooth muscle. Fundam Clin Pharmacol 2010; 25:690-9. [DOI: 10.1111/j.1472-8206.2010.00892.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Xu L, Ting-Lou, Lv N, Zhu X, Chen Y, Yang J. Emodin augments calcium activated chloride channel in colonic smooth muscle cells by Gi/Go protein. Eur J Pharmacol 2009; 615:171-6. [PMID: 19409890 DOI: 10.1016/j.ejphar.2009.04.045] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2008] [Revised: 04/12/2009] [Accepted: 04/20/2009] [Indexed: 10/20/2022]
Abstract
Emodin is a natural anthraquinone in rhubarb. It has been identified as a prokinetic drug for gastrointestinal motility in Chinese traditional medicine. Emodin contracts smooth muscle by increasing the concentration of intracellular Ca(2+). In many smooth muscles, increasing intracellular Ca(2+) activates Ca(2+)-activated Cl(-) channels (ClCA). The study was aimed to investigate the effects of emodin on ClCA channels in colonic smooth muscle. 4 channel physiology signal acquire system was used to measure isometric contraction of smooth muscle strips. ClCA currents were recorded by EPC10 with perforated whole cell model. Emodin contracted strips and cells in colonic smooth muscle and augmented ClCA currents. Niflumic acid (NFA) and 4', 4'-diisothiostilbene-2, 2-disulfonic acid (DIDS) blocked the effects. Gi/Go protein inhibits protein kinase A (PKA) and protein kinase C (PKC), and PKA and PKC reduced ClCA currents. Pertussis toxin (PTX, a special inhibitor of Gi/Go protein), 8-bromoadenosine 38, 58-cyclic monophosphate (8-BrcAMP, a membrane-permeant protein kinase A activator) and Phorbol-12-myristate-13-acetate (PMA, a membrane-permeant protein kinase C activator) inhibited the effects on ClCA currents significantly. Our findings suggest that emodin augments ClCA channels to contract smooth muscle in colon, and the effect is induced mostly by enhancement of membrane Gi/Go protein signal transducer pathway.
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Affiliation(s)
- Long Xu
- Department of gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China
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