期刊
PEPTIDES
卷 31, 期 6, 页码 1062-1067出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2010.03.008
关键词
PACAP; Cyclization; PAC1; Agonist; STZ-induced diabetes
资金
- Guangdong Provincial Nature Science Funding of China [06300579]
- Science Technology Research Key Project of the Educational Department of China [207141]
- Nature Science Funding of China [30973244]
The N-terminal deletion of pituitary adenylate cyclase-activating polypeptide (PACAP)(1-5) generates its own antagonist. The cyclopeptide C*HSDGIC*, which results from the cyclization of PACAP(1-5) with disulfide, was designed and synthesized. CHO cells expressing a PAC1 N/R splice variant (PAC1-CHO) were used to detect the potent activation of PAC1 by C*HSDGIC*. In vitro cell assays showed that C*HSDGIC* stimulated cAMP production and increased the viability of PAC1-CHO cells at micromolar concentrations, about 1000 fold that of PACAP. PACAP(6-38) blocked the effects of PACAP on the proliferation of PAC1-CHO cells but did not interfere with the effects of C*HSDGIC*, suggesting that the activation of PAC1 by C*HSDGIC* was independent of the binding of PAC1 to the C-terminus of PACAP. In experiments in vivo, 10 mu mol/kg C*HSDGIC* decreased the plasma glucose level, increased the plasma insulin level and improved glucose tolerance significantly (P < 0.01) when co-injected with STZ for 5 days. The results of these in vitro and in vivo studies of the biological characteristics of C*HSDGIC* reveal that it is a potent activator of PAC1. (C) 2010 Elsevier Inc. All rights reserved.
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