Lee B, Yang C, Chen T H, al-Azawi N, Hsu W H
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011, USA.
Am J Physiol. 1995 Dec;269(6 Pt 1):E1095-100. doi: 10.1152/ajpendo.1995.269.6.E1095.
We used a number of receptor antagonists to determine which receptors mediate the effect of arginine vasopressin (AVP) and oxytocin (OT) on insulin release. We found that OT (10(-7) M) and AVP (10(-8) M) increased insulin release from the perfused rat pancreas with similar magnitude. The antagonist with potent V1b receptor-blocking activity, dP[Tyr(Me)2]AVP (10(-7) M), abolished the effect of OT and AVP, whereas the highly selective OT receptor antagonist L-366,948 (10(-6) M) did not change the effect of OT, nor did a V1a receptor antagonist, d(CH2)5[Tyr(Me)2]AVP (10(-7) M), change the effect of AVP. The insulin-releasing potency of OT was estimated as 9-fold less than that of AVP in RINm5F cells. Selected AVP and OT antagonists were used to study their antagonism on AVP- and OT-induced insulin release from RINm5F cells, and the order of potencies of antagonists was estimated as dP[Tyr(Me)2]AVP > d(CH2)5[D-Phe2,Ile4]AVP > SR-49059 > d(CH2)5[Tyr(Me)2]AVP > desGly9d(CH2)5[Tyr(Et)2]VAVP (WK-3-6) approximately L-366,948. These results were consistent with the V1b receptor antagonistic activities of the antagonists. d[D-3-Pal]VP, a V1b receptor agonist, increased insulin release dose dependently (10(-9) to 10(-6) M), and this effect was antagonized by dP[Tyr(Me)2]AVP but not by WK-3-6 (10(-6) M). These results suggested that the stimulatory effect of both OT and AVP on insulin release from beta-cells may be mediated by V1b, but not by V1a or OT receptors.
我们使用了多种受体拮抗剂来确定哪些受体介导精氨酸加压素（AVP）和催产素（OT）对胰岛素释放的作用。我们发现，OT（10⁻⁷ M）和AVP（10⁻⁸ M）使灌注大鼠胰腺的胰岛素释放增加，幅度相似。具有强效V1b受体阻断活性的拮抗剂dP[Tyr(Me)2]AVP（10⁻⁷ M）消除了OT和AVP的作用，而高度选择性的OT受体拮抗剂L-366,948（10⁻⁶ M）并未改变OT的作用，V1a受体拮抗剂d(CH2)5[Tyr(Me)2]AVP（10⁻⁷ M）也未改变AVP的作用。在RINm5F细胞中，OT的胰岛素释放效力估计比AVP低9倍。选用AVP和OT拮抗剂研究它们对RINm5F细胞中AVP和OT诱导的胰岛素释放的拮抗作用，拮抗剂效力顺序估计为dP[Tyr(Me)2]AVP > d(CH2)5[D-Phe2,Ile4]AVP > SR-49059 > d(CH2)5[Tyr(Me)2]AVP > desGly9d(CH2)5[Tyr(Et)2]VAVP（WK-3-6）≈ L-366,948。这些结果与拮抗剂的V1b受体拮抗活性一致。V1b受体激动剂d[D-3-Pal]VP剂量依赖性地增加胰岛素释放（10⁻⁹至10⁻⁶ M），且该作用被dP[Tyr(Me)2]AVP拮抗，但不被WK-3-6（10⁻⁶ M）拮抗。这些结果表明，OT和AVP对β细胞胰岛素释放的刺激作用可能由V1b介导，而非V1a或OT受体。
