Bimodal regulation of pancreatic exocrine function in vitro by somatostatin-28.
The action of natural and synthetic somatostatin-(1--28), [Nle8]somatostatin-(1--28), somatostatin-(15--28), and somatostatin-(1--14) was examined in dispersed acini from guinea pig pancreas. At high concentrations, the 28-amino acid form of somatostatin increased amylase release, outflux of 45Ca, cellular cGMP, and to a lesser extent cellular cAMP. The increase in amylase release was suppressed by dibutyryl cGMP but was not modified by theophylline or atropine. Binding of 125I-labeled [Thr28, Nle31] cholecystokinin-(25--33) was inhibited by [Nle8]somatostatin-(1--28). These effects required the entire 28-amino acid peptide and appeared to result from occupation of cholecystokinin receptors. It is postulated that they involve interactions between the C-terminal and the N-terminal sequences of the molecule with the participation of the amino acid in position 8. At low concentrations, natural and synthetic forms of somatostatin-(1--28) and somatostatin-(15--28) inhibited secretin- and vasoactive intestinal peptide (VIP)-stimulated increases in cellular cAMP concentration. No difference was found between the potency of somatostatin peptides, indicating that the tetradecapeptide somatostatin-(15--28) is sufficient to exert an inhibitory action on secretin- and VIP-stimulated cellular cAMP concentration. By contrast, the somatostatin fragment S-(1--14) was inactive on pancreatic cellular function.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002108:Ceruletide / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000502:physiology*; D011498:Protein Precursors / Q000494:pharmacology*; D012633:Secretin / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology*; D053561:Somatostatin-28; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D011498:Protein Precursors; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D053561:Somatostatin-28; D002108:Ceruletide; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D000681:Amylases; D006152:Cyclic GMP; D002118:Calcium