Brief Article
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World J Gastroenterol. Oct 14, 2010; 16(38): 4865-4870
Published online Oct 14, 2010. doi: 10.3748/wjg.v16.i38.4865
Possible key residues that determine left gastric artery blood flow response to PACAP in dogs
Mu-Xin Wei, Ping Hu, Ping Wang, Satoru Naruse, Kiyoshi Nokihara, Victor Wray, Tsuyoshi Ozaki
Mu-Xin Wei, Ping Hu, Ping Wang, Department of Traditional Chinese Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Satoru Naruse, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Kiyoshi Nokihara, Hipep Laboratories, Nakatsukasa-cho, 486-46, Kamigyo-ku, Kyoto 602-8158, Japan
Victor Wray, Department of Structural Biology, Helmholtz Centre for Infection Research, 3300 Braunschweig, Germany
Tsuyoshi Ozaki, National Institute of Physiological Sciences, Okazaki 444-8787, Japan
Author contributions: Wei MX, Naruse S and Nokihara K designed the research; Ozaki T provided the experimental tools and chemicals; Wray V provided the reagents and did the structure analysis; Hu P and Wang P analyzed the data and wrote the paper.
Supported by (in part) Grants from Ministry of Education, Culture, Science, and Technology, Japan Society for the Promotion of Science and Special Fund of Six-Talented Peak of Jiangsu Province, No. 07-B-15 (IB07)
Correspondence to: Dr. Mu-Xin Wei, Department of Traditional Chinese Medicine, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, China. weimuxin@njmu.edu.cn
Telephone: +86-25-83718836-6267 Fax: +86-25-83724440
Received: May 11, 2010
Revised: June 18, 2010
Accepted: June 25, 2010
Published online: October 14, 2010
Abstract

AIM: To determine the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on left gastric artery (LGA) flow and to unveil the structural or functional important sites that may be critical for discrimination of different receptor subtypes.

METHODS: Peptides, including PACAP-27, PACAP-38, amino acid substituted PACAP-27 and C-terminus truncated analogues PACAP (27-38), were synthesized by a simultaneous multiple solid-phase peptide synthesizer. Flow probes of an ultrasound transit-time blood flowmeter were placed around the LGA of beagle dogs. When peptides were infused intravenously, the blood flow was measured.

RESULTS: [Ala4, Val5]-PACAP-27 caused a concentration-dependent vasodepressor action which was similar to that caused by PACAP-27. The LGA blood flow response to [Ala4, Val5]-PACAP-27 was significantly higher than that to PACAP-27, which was similar to that to vasoactive intestinal polypeptide (VIP) at the same dose. [Ala6]-PACAP-27 did not increase the peak LGA flow. [Gly8]-PACAP-27 showed a similar activity to VIP. [Asn24, Ser25, Ile26]-PACAP-27 did not change the activity of peptides at all doses.

CONCLUSION: NH2 terminus is more important to biological activity of peptides and specific receptor recognition than COOH-terminus.

Keywords: Pituitary adenylate cyclase-activating polypeptide; Pituitary adenylate cyclase-activating polypeptide 27; Pituitary adenylate cyclase-activating polypeptide P38; Left gastric artery; Blood flow