Cerebral Vascular Adenylate Cyclase: Evidence for Coupling to Receptors for Vasoactive Intestinal Peptide and Parathyroid Hormone
Cerebral Vascular Adenylate Cyclase: Evidence for Coupling to Receptors for Vasoactive Intestinal Peptide and Parathyroid Hormone
复制标题
脑血管腺苷酸环化酶：与血管活性肠肽和甲状旁腺激素受体偶联的证据
作者：
Minta Huang;O. Rorstad
摘要：我们用脑微血管和动脉标本研究了血管腺苷酸环化酶对血管活性肠肽（VIP）和甲状旁腺激素（PTH）的反应性。从大鼠、豚鼠、牛和猪中获得的脑微血管均对牛（B）PTH-（1 - 34）产生有效反应，而在对VIP的反应性中观察到相当大的种属间差异。VIP的同源肽，PHI（猪七肽），刺激大鼠微血管和牛动脉的破碎细胞制备物中的腺苷酸环化酶。VIP、PHI和bPTH-（1 - 34）激活牛动脉腺苷酸环化酶的ED 50值分别为6.9 nM、10 nM和100 nM，效力顺序如下：VIP = PHI > bPTH-（1 - 34）。其他相关肽hpGRF（人胰腺生长激素释放因子）、胰泌素和胰高血糖素以及片段VIP-（10 - 28）无活性。PTH拮抗剂[Nle 8，Nle 18，Tyr 34]bPTH-（3 - 34）酰胺可抑制bPTH-（1 - 34）对血管腺苷酸环化酶的激活，但不影响VIP对微血管或动脉的激活。VIP或PHI与bPTH-（1 - 34）对血管腺苷酸环化酶活性具有累加效应。而VIP和PHI的作用是非加和的。这些数据表明VIP和bPTH-（1 - 34）通过与不同的受体相互作用激活脑血管腺苷酸环化酶，而PHI和VIP可能与共同的受体相互作用。
Abstract: We have studied the responsiveness of vascular adenylate cyclase to vasoactive intestinal peptide (VIP) and parathyroid hormone (PTH) using preparations of cerebral microvessels and arteries. Cerebral microvessels obtained from rats, guinea‐pigs, cattle, and pigs all responded potently to bovine (b) PTH‐(1‐34), whereas considerable between‐species variability was observed in the responsiveness to VIP. The homologous peptide to VIP, PHI (porcine heptacosapeptide), stimulated adenylate cyclase in both rat microvessels and a broken‐cell preparation of bovine arteries. The ED50 values for activation of bovine arterial adenylate cyclase by VIP, PHI, and bPTH‐(1‐34) were 6.9 nM, 10 nM, and 100 nM, respectively, with the following order of efficacy: VIP = PHI > bPTH‐(1‐34). The other related peptides, hpGRF (human pancreatic growth hormone releasing factor), secretin, and glucagon, and the fragment VIP‐(10‐28) were inactive. The PTH antagonist, [Nle8, Nle18, Tyr34]bPTH‐(3‐34) amide, inhibited bPTH‐(1‐34) activation of vascular adenylate cyclase but did not affect activation by VIP using either microvessels or arteries. VIP or PHI demonstrated an additive effect with bPTH‐(1‐34) on vascular adenylate cyclase activity. However, the effects of VIP and PHI were nonadditive with each other. These data suggest that VIP and bPTH‐(1‐34) activate cerebral vascular adenylate cyclase by interacting with pharmacologically distinct receptors, whereas PHI and VIP likely interact with a common receptor.