Secretin induces rapid increases in inositol trisphosphate, cytosolic Ca2+ and diacylglycerol as well as cyclic AMP in rat pancreatic acini

Author:

Trimble E R,Bruzzone R,Biden T J,Farese R V

Abstract

Previous studies have shown that the dose-response relationship for secretin-stimulated cyclic AMP accumulation is different from that for secretin-stimulated enzyme secretion in the rat exocrine pancreas. Here we show that secretin concentrations of 10(-10) M and higher stimulated a rise in cyclic AMP levels, with maximum effect on cyclic AMP accumulation being achieved already with 10(-8) M-secretin. However, at this concentration of secretin, enzyme secretion rates were approximately half-maximal. Unexpectedly, at concentrations of secretin greater than 10(-8) M there was evidence suggestive of phosphatidylinositol bisphosphate hydrolysis with rapid increases in inositol trisphosphate, cytosolic free calcium and diacylglycerol content of rat pancreatic acini. Furthermore, there was a dose-response relationship among secretin concentration (in the range 10(-8) M-2 × 10(-6) M), increases in inositol trisphosphate and increases in cytosolic free calcium ([Ca2+]i). Contrary to what has been previously believed, these results clearly indicate that in rat pancreatic acini secretin not only stimulates cyclic AMP accumulation but also raises inositol trisphosphate, [Ca2+]i and diacylglycerol. Thus, two second messenger systems may play a role in the regulation of secretin-induced amylase release.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

Cited by 49 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Occupancy of both sites on the thyrotropin (TSH) receptor dimer is necessary for phosphoinositide signaling;The FASEB Journal;2011-06-24

2. Secretin: Should we revisit its metabolic outcomes?;Journal of Endocrinological Investigation;2010-04

3. Differential effects of secretin-fragments imply a dual mechanism of action for secretin;International Journal of Peptide and Protein Research;2009-01-12

4. Multiple Actions of Secretin in the Human Body;International Review of Cytology;2008

5. Signaling mechanisms of secretin receptor;Regulatory Peptides;2006-11

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