PANCREATIC CHANGES IN SOMATOSTATIN CONTENT AND RECEPTOR-EFFECTOR SYSTEM AFTER INTRAPANCREATIC INJECTION OF 5,7-DIHYDROXYTRYPTAMINE

To date, it is unknown whether intrapancreatic serotonergic nerves can influence pancreatic somatostatin (SS) content and the SS receptor/ef fector system in the exocrine pancreas. In this study, the intrapancre atic serotonergic nerves were chemically ablated by injecting a specif ic serotonin (5-HT) neurotoxin, 5,7-dihydroxy-tryptamine (5,7-DHT), in to the substance of the gland. Three days after the injection, the 5-H T-like immunoreactive levels in the pancreas were reduced by more than 85% whereas somatostatin-like immunoreactive levels had increased (86 %). The number of SS receptors in the pancreatic acinar cell membranes of the 5,7-DHT-treated rats was also increased (72%). No significant differences were seen in basal or forskolin-stimulated adenylate cycla se (AC) enzyme activities in the control and the 5,7-DHT-treated group s. In spite of the increase in the number of SS receptors in the pancr eatic acinar cell membranes of 5,7-DHT-treated rats, SS caused a signi ficantly lower inhibition of AC activity in these membranes. This find ing is related to the observed decrease of a 41 kD pertussis toxin-sen sitive substrate, presumably the alpha(i) subunit of the guanine nucle otide inhibitory protein, in pancreatic acinar cell membranes 3 days a fter intrapancreatic 5,7-DHT administration when compared with the cor responding controls. The functions of pancreatic serotonergic nerves s eem to be associated with enteropancreatic communication. These data t ogether with the present results suggest that pancreatic SS content an d the SS receptor/effector system in the exocrine pancreas may be regu lated by enteropancreatic serotonergic nerve fibers and may participat e in enteropancreatic reflexes.