Effects of arginine vasopressin and oxytocin on glucagon release from clonal alpha-cell line In-R1-G9: involvement of V1b receptors.

Receptor antagonists were used to determine which receptor mediates the effect of arginine vasopressin (AVP) and oxytocin (OT) on glucagon release from hamster glucagonoma In-R1-G9 cells. Both AVP (10(-9)-10(-6) M) and OT (10(-8)-10(-5) M) increased glucagon release from In-R1-G9 cells in a concentration-dependent manner and AVP was approximately 30-fold more potent than OT in this aspect. The antagonists with potent V1b receptor blocking activity, CL-4-84 (10(-9)-10(-6) M), dP[Tyr(Me)2]AVP and AO-2-44 (10(-8)-10(-6) M), antagonized the effect of both AVP and OT in a concentration-dependent manner. Other receptor antagonists at 10(-6) M failed to block the effect of AVP and OT; these included a highly selective OT-receptor antagonist, L-366,948 and a V1a/V2 receptor antagonist WK-3-6. However, these antagonists at higher concentrations (10(-5) and 10(-4) M) caused inhibition of AVP- and OT-induced glucagon release. The order of antagonistic potency was estimated as CL-4-84 approximately = dP[Tyr(Me)2]AVP approximately = AO-2-44 > WK 3-6 > L366,948. d[D-3-Pal]VP (10(-8)-10(-5) M), a V1b receptor agonist, also increased glucagon release in a concentration-dependent manner, which was antagonized by dP[Tyr(Me)2]AVP (10(-8)-10(-6) M) and CL-4-84 (10(-9)-10(-6) M), but not by WK-3-6 (10(-6) M) or L-366,948 (10(-6) M). Therefore, the stimulatory effects of both OT and AVP on glucagon release may be mediated by V1b receptors, but not by V1a, V2, or OT receptors.