Fujiwara Yoko, Hiroyama Masami, Sanbe Atsushi, Yamauchi Junji, Tsujimoto Gozoh, Tanoue Akito
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
J Endocrinol. 2007 Feb;192(2):361-9. doi: 10.1677/joe.1.06864.
[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.
[精氨酸8] - 加压素（AVP）和催产素（OT）是神经垂体激素，在一些外周组织中发挥多种作用，包括对血糖的控制。为了研究参与AVP和OT诱导的胰高血糖素分泌的受体类型，我们研究了这些肽对野生型（V1bR + / +）和血管加压素V1b受体敲除（V1bR - / -）小鼠胰岛中胰高血糖素分泌的影响。在V1bR + / +小鼠的胰岛中，选择性V1b受体拮抗剂SSR149415显著抑制AVP诱导的胰高血糖素分泌（30%），特异性OT受体拮抗剂d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH(2)(9)]OVT（CL - 14 - 26）显著抑制OT诱导的胰高血糖素分泌（45%）。AVP和OT诱导的胰高血糖素分泌不受各自拮抗剂的抑制，但10(-6) M SSR149415和10(-6) M CL - 14 - 26共同孵育进一步抑制V1bR + / +小鼠胰岛中AVP和OT诱导的胰高血糖素分泌（分别为刺激值的57%和69%）。此外，AVP和OT在V1bR - / -小鼠中刺激胰高血糖素分泌的效力与在V1bR + / +小鼠中相同。CL - 14 - 26显著抑制V1bR - / -小鼠中AVP和OT诱导的胰高血糖素分泌。这些结果表明，在存在异源拮抗剂的情况下，V1b受体可介导V1bR + / +小鼠胰岛中OT诱导的胰高血糖素分泌，OT受体可介导AVP诱导的胰高血糖素分泌，而AVP和OT可通过V1bR - / -小鼠中的OT受体刺激胰高血糖素分泌，这表明当一种受体缺失时，另一种受体可以起到补偿作用。
