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Published on: October 14, 2016
Possible key residues that determine left gastric artery blood flow response to PACAP in dogs
Mu-Xin Wei1, Ping Hu, Ping Wang
1Department of Traditional Chinese Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. weimuxin@njmu.edu.cn
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.
