Characterization of receptors mediating AVP- and OT-induced glucagon release from the rat pancreas.
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 V(1b) 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(CH(2))(5)[Tyr(Me)(2)]AVP (10 nM), a V(1a) 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 microM 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 V(1b) and OT receptors, respectively.
Yibchok-Anun
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S
Department of Biomedical Sciences, Iowa State University, Ames, Iowa 50011, USA.
Cheng
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H
Heine
P A
PA
Hsu
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WH
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000502:physiology*; D017483:Receptors, Vasopressin / Q000502:physiology*
D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; C098114:hydroxyphenylacetyl-methyltyrosyl-phenylalanyl-glutaminyl-asparaginyl-arginyl-prolyl-argininamide; D001127:Arginine Vasopressin; C066873:L 366948; D010121:Oxytocin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D005934:Glucagon