Characterization of receptors mediating AVP- and OT-induced glucagon release from the rat pancreas

Abstract

We characterized the receptors that mediate arginine vasopressin (AVP)- and oxytocin (OT)-induced glucagon release by use of a number of antagonists in the perfused rat pancreas and the fluorescence imaging of the receptors. AVP and OT (3 pM-3 nM) increased glucagon release in a concentration-dependent manner. The antagonist with potent V1b receptor-blocking activity, CL-4–84 (10 nM), abolished AVP (30 pM)-induced glucagon release but did not alter OT (30 pM)-induced glucagon release. d(CH2)5[Tyr(Me)2]AVP (10 nM), a V1a receptor antagonist, and L-366,948 (10 nM), a highly specific OT-receptor antagonist, failed to inhibit AVP-induced glucagon release. In contrast, L-366,948 (10 nM) abolished OT (30 pM)-induced glucagon release but did not change the effect of AVP. Fluorescent microscopy of rat pancreatic sections showed that fluorescence-labeled AVP and OT bound to their receptors in the islets of Langerhans and that the bindings were inhibited by 1 μM of Cl-4–84 and L-366,948, respectively. Because AVP and OT at physiological concentrations (3–30 pM) increased glucagon release, we conclude that AVP and OT increase glucagon release under the physiological condition through the activation of V1b and OT receptors, respectively.