title: Mutual regulation of vasopressin- and oxytocin-induced glucagon secretion in V1b vasopressin receptor knockout mice.
abstract: [Arg8]-vasopressin (AVP) and oxytocin (OT) are neurohypophysial hormones which exert various actions, including the control of blood glucose, in some peripheral tissues. To investigate the type of receptors involved in AVP- and OT-induced glucagon secretion, we investigated the effect of these peptides on glucagon secretion in islets of wild-type (V1bR+/+) and vasopressin V1b receptor knockout (V1bR-/-) mice. AVP-induced glucagon secretion was significantly inhibited by the selective V1b receptor antagonist, SSR149415 (30%), and OT-induced glucagon secretion by the specific OT receptor antagonist, d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH(2)(9)]OVT (CL-14-26) (45%), in islets of V1bR+/+mice. AVP- and OT-induced glucagon secretions were not by the antagonist of each, but co-incubation with both 10(-6) M SSR149415 and 10(-6) M CL-14-26 further inhibited AVP- and OT-induced glucagon secretions in islets of V1bR+/+ mice (57 and 69% of the stimulation values respectively). In addition, both AVP and OT stimulated glucagon secretion with the same efficacy in V1bR-/- mice as in V1bR+/+ mice. AVP- and OT-induced glucagon secretion in V1bR-/- mice was significantly inhibited by CL-14-26. These results demonstrate that V1b receptors can mediate OT-induced glucagon secretion and OT receptors can mediate AVP-induced glucagon secretion in islets from V1bR+/+mice in the presence of a heterologous antagonist, while AVP and OT can stimulate glucagon secretion through the OT receptors in V1bR-/-mice, suggesting that the other receptor can compensate when one receptor is absent.
authors.affiliation: Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Masami
authors.initials: M
authors.lastname: Hiroyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sanbe
authors.forename: Junji
authors.initials: J
authors.lastname: Yamauchi
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001681:Biological Assay / Q000379:methods; D005260:Female; D005934:Glucagon / Q000032:analysis / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010121:Oxytocin / Q000031:analogs & derivatives / Q000494:pharmacology*; D011485:Protein Binding; D011759:Pyrrolidines / Q000494:pharmacology; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D017483:Receptors, Vasopressin / Q000502:physiology*; D013268:Stimulation, Chemical; D046509:Tissue Culture Techniques
chemical_list: C456029:1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide; D065092:Antidiuretic Hormone Receptor Antagonists; D007211:Indoles; C055830:KB 5-21; D011759:Pyrrolidines; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D010121:Oxytocin; D005934:Glucagon