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.
Yibchok-anun
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Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames 50011, USA.
Hsu
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WH
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism*; D005935:Glucagonoma / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000145:classification / Q000378:metabolism*; D012076:Renal Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D010456:Peptides, Cyclic; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D012076:Renal Agents; D001127:Arginine Vasopressin; C066873:L 366948; D010121:Oxytocin; D005934:Glucagon