5-Hydroxytryptamine decreases somatostatin receptors and somatostatin-responsive adenylyl cyclase in rat pancreatic acinar membranes

Abstract

Pretreatment of pancreatic acini with 5-hydroxytryptamine (5-HT) reduced the binding of the labeled somatostatin (SS) analogue 125I-Tyr3-SMS to pancreatic acinar membranes. This effect was dependent of the dose of 5-HT used and length of pretreatment. This inhibitory effect of 5-HT was abolished when pancreatic acini were pretreated with 5-HT in the presence of the 5-HT1P receptor-antagonist 5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP). Pretreatment of pancreatic acini with 5-HT reduced the inhibition by the stable SS analogue SMS 201-995 of basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity in pancreatic acinar membranes. There was no statistical difference established between IC50 values for the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) which inhibits ligand binding to SMS receptors in controls and in 5-HT treated pancreatic cells, respectively. In addition, no significant differences were seen in the level of Gi proteins in the control and 5-HT treated panceatic acini. These data suggest that the decrease of the number of 125I-Tyr3-SMS receptors, would explain the decreased sensitivity of AC to SMS 201-995 in membranes from 5-HT-pretreated acini.