Wei MX, Naruse S, Nokihara K, Ozaki T, Ando E, Wray V. Structure-activity relationship of pituitary adenylate cyclase activating polypeptide. World J Gastroenterol 1996; 2(3): 131-133 [DOI: 10.3748/wjg.v2.i3.131]
Corresponding Author of This Article
Dr. Mu-Xin Wei, Associate Professor, Department of TCM, 1st College of Clinical Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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Experimental Papers
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World J Gastroenterol. Sep 15, 1996; 2(3): 131-133 Published online Sep 15, 1996. doi: 10.3748/wjg.v2.i3.131
Structure-activity relationship of pituitary adenylate cyclase activating polypeptide
Mu-Xin Wei, S Naruse, K Nokihara, T Ozaki, E Ando, V Wray
Mu-Xin Wei, Department of TCM, 1st College of Clinical Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
S Naruse, Department of Internal Medicine 2, Nagoya University School of Medicine, Nagoya 466, Japan
K Nokihara, E Ando, Biotechnology Instruments Department, Shimadzu Corp., Kyoto 604, Japan
T Ozaki, National Institute for Physiological Sciences, Okazaki 444, Japan
V Wray, Gesellschaft FüR Biotechnologische Forschung, Braunschweig D 38124, Germany
Mu-Xin Wei, Associate Professor of TCM, a visiting scientist of National Institute for Physiological Sciences in Japan 1992-1996, having 40 papers published.
Author contributions: All authors contributed equally to the work.
Supported by Monbusho international scientific research program and a grant from the Ministry of Education, Science and Culture, Japan to Dr. Naruse S.
Correspondence to: Dr. Mu-Xin Wei, Associate Professor, Department of TCM, 1st College of Clinical Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Telephone: +86-25-6600261 Fax: +86-25-6508960
Received: July 28, 1996 Revised: August 13, 1996 Accepted: September 2, 1996 Published online: September 15, 1996
Abstract
AIM: To investigate the structure-activity relationship of pituitary adenylate cyclase activating polypeptide (PACAP) in guinea pig gallbladder using a synthetic PACAP/vasoactive intestinal peptide (VIP) hybrid.
METHODS: We synthesized PACAP-VIP hybrid peptides using the Fmoc strategy and a simultaneous multiple solid-phase peptide synthesizer. The peptides were tested in isolated guinea pig gallbladders using an improved horizontal type organ bath.
RESULTS: VIP induced relaxation of gallbladder smooth muscle strips, while PACAP27 contracted them. Amino acids at positions 4, 5, 9, and 24-26 were replaced without significant loss of activity. [Leu13]-PACAP27, a substitution in the α-helix domain, also had no significant loss in activity (P < 0.05). It was more potent than [Gly8]- and [DAsp8]-PACAP27 and could substitute peptides at position 21. Des-[His1] and [Ala6]-PACAP27 had no activity at 10-7 mol/L. [Gly8]-, [DAsp8]-, [Phe21]- and [Pro21]-PACAP27 at 10-7 mol/L had about 25% of the activity of PACAP27 at 10-7 mol/L (P < 0.05).
CONCLUSION: The N-terminal disordered region is more important than other regions for determining the physiological activity of PACAP in the guinea pig gallbladder.
