COMPARATIVE EFFECTS OF PACAP AND VIP ON PANCREATIC ENDOCRINE SECRETIONS AND VASCULAR-RESISTANCE IN RAT

1 The effects of pituitary adenylate cyclase-activating polypeptide (P ACAP), vasoactive intestinal peptide (VIP) and secretin on pancreatic endocrine secretions and vascular resistance were investigated and com pared in the isolated perfused pancreas of the rat. The PACAP/VIP rece ptor types involved have been characterized. 2 On insulin secretion, i n the range 10(-11) to 10(-8) M, PACAP and VIP elicited a concentratio n-dependent biphasic response from pancreas perfused with 8.3 mM gluco se; the peptides were equipotent. In contrast, secretin was ineffectiv e in the range 10(-11) to 10(-9) M; at 10(-8) and 10(-7) M, it induced only low and transient insulin responses. On the other hand, the pept ides did not modify the basal insulin release in the presence of a non stimulating glucose concentration (2.8 mM). 3 On glucagon secretion, PACAP and VIP (10(-11) to 10(-8) M) but also secretin (10(-9) to 10(-7 ) M) caused a concentration-dependent peak shaped response from pancre as perfused with 2.8 mM glucose; PACAP and VIP were equipotent and 20 times more potent than secretin. On the other hand, the peptides did n ot affect the glucagon release in the presence of 8.3 mM glucose. 4 On pancreatic vessels, in the range 10(-11) to 10(-9) M, the three pepti des were equipotent in inducing a concentration-dependent sustained in crease in pancreatic flow rate. On the other hand, at the high concent ration of 10(-7) M PACAP but not VIP provoked a transient decrease of flow rate. 5 This study provides evidence for PACAP/VIP type II recept ors mediating insulin and glucagon secretion as well as vasodilatation in rat pancreas. In addition, the different efficacies of secretin su ggest that these effects are mediated by different PACAP/VIP type II r eceptor subtypes.