Effect of somatostatin on cholecystokinin-induced amylase release in rat pancreatic acini

• Published in: Pancreas Vol. 23; no. 1; p. 102
• Main Authors: Rhie, D J, Kim, M J, Choi, W S, Lee, K H, Sung, J H, Min, D S, Yoon, S H, Hahn, S J, Kim, M S, Jo, Y H
• Format: Journal Article
• Language: English
• Published: United States 01.07.2001
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Amylases - metabolism; Animals; Calcium Signaling - drug effects; Cell-Free System; Colforsin - pharmacology; Cyclic AMP - biosynthesis; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Inositol Phosphates - biosynthesis; MAP Kinase Signaling System - drug effects; Octreotide - pharmacology; Pancreas - drug effects; Pancreas - metabolism; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - physiology; Rats; Second Messenger Systems - drug effects; Secretory Rate - drug effects; Sincalide - pharmacology; Sodium Fluoride - pharmacology; Somatostatin - pharmacology; Tungsten Compounds - pharmacology
• ISSN: 0885-3177
• DOI: 10.1097/00006676-200107000-00015

The effect of somatostatin on cholecystokinin-induced amylase release was investigated in isolated rat pancreatic acini. Acini were isolated by enzymatic digestion and incubated in a HEPES buffered Ringer's solution with testing reagents for 30 minutes at 37 degrees C. The activity of released amylase, cAMP, and inositol phosphate formation were measured. Intracellular calcium concentration ([Ca2+]i) was also checked. Somatostatin 14 and octreotide, a somatostatin analog, inhibited CCK-stimulated amylase release in a concentration-dependent manner. The inhibitory effect of octreotide on CCK-induced amylase release was not shown when the acini were treated with 8-Br-cAMP, irrespective of the presence of IBMX. Forskolin potentiated CCK-induced amylase release and this effect was blocked by octreotide treatment; although CCK-8 (3 x 10(-11) M) failed to stimulate cAMP formation, octreotide significantly inhibited basal cAMP formation in the acini. The increase of [Ca2+]i in response to CCK was inhibited by octreotide. However, CCK-induced inositol phosphate formation was not changed by 10(-9) M octreotide. Octreotide had no effect on CCK-stimulated tyrosine phosphorylation, and tyrosine phosphatase inhibitors (NaF and Na2WO4) did not influence the effect of octreotide on CCK-induced amylase release. From these results, we conclude that octreotide inhibits CCK-induced amylase release by inhibiting basal cAMP formation and decreasing the [Ca2+]i stimulated by CCK.