Inhibitory actions of a somatostatin analog SMS 201-995 on endocrine secretion from the isolated perfused stomach and pancreas of the rat.
An analog of somatostatin, SMS 201-995 (SMS; Sandostatin), has been shown to have increased potency in the inhibition of hormone secretion in vivo. In this study, the effect of SMS on the secretion of immunoreactive insulin, gastrin and gastric somatostatin was examined in the rat using in situ vascularly perfused organ preparations. The analog was found to inhibit both basal somatostatin and gastrin secretion from the perfused stomach in a concentration-dependent manner. SMS (9.4 x 10(-8) mol/l) also inhibited somatostatin release stimulated by gastric inhibitory polypeptide (GIP), but did not suppress gastrin release under the same conditions; an opposite effect was obtained when l-isoproterenol was used to stimulate somatostatin release. In the perfused pancreas both SS-14 (6.1 x 10(-9) mol/l) and SMS (9.4 x 10(-9) mol/l) inhibited the GIP (2 x 10(-9) mol/l) or acetylcholine (1 x 10(-6) mol/l), but not 17.8 x 10(-9) mol/l glucose-stimulated insulin secretion. Insulin secretion stimulated by 17.8 x 10(-3) mol/l glucose was unaffected by either peptide at this concentration. These results show that SMS is a potent inhibitor of gastric and pancreatic endocrine secretion. However, the inhibitory effect of SMS on gastric endocrine secretion was uncoupled in the presence of different secretagogues, suggesting that the action of SMS was dependent on the activation of different mechanisms or pathways in the stomach. In the pancreas, SMS appears to be acting on the beta-cell via a similar mechanism as somatostatin.
Verchere
C B
CB
Department of Physiology, University of British Columbia, Vancouver, Canada.
Kwok
Y N
YN
Brown
J C
JC
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism*
D005755:Gastrins; D007328:Insulin; D013004:Somatostatin; D007545:Isoproterenol; D015282:Octreotide