5-HYDROXYTRYPTAMINE DECREASES SOMATOSTATIN RECEPTORS AND SOMATOSTATIN-RESPONSIVE ADENYLYL-CYCLASE IN RAT PANCREATIC ACINAR MEMBRANES

Pretreatment of pancreatic acini with 5-hydroxytryptamine (5-HT) reduc ed the binding of the labeled somatostatin (SS) analogue I-125-Tyr(3)- SMS to pancreatic acinar membranes. This effect was dependent of the d ose 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 w ith 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 es tablished between IC50 values for the stable GTP analogue 5'-guanylyli midodiphosphate (Gpp(NH)p) which inhibits Ligand binding to SMS recept ors in controls and in 5-HT treated pancreatic cells, respectively. In addition, no significant differences were seen in the level of Gi pro teins in the control and 5-HT treated pancreatic acini. These data sug gest that the decrease of the number of I-125-Tyr(3)-SMS receptors, wo uld explain the decreased sensitivity of AC to SMS 201-995 in membrane s from 5-HT-pretreated acini.