NEUROHYPOPHYSEAL PEPTIDES AND ETHANOL TOLERANCE

精氨酸加压素(AVP)及相关多肽，何时 外源性给药，延长耐受期 乙醇。神经垂体肽的相似性 对耐受性的影响和先前报道的对记忆的影响 整合支持了这样的假设，即这些现象可能 共享底层机制。使用多肽激动剂 选择性地与加压素V1和V2受体相互作用 已将大脑中的受体定性为V1，这些受体介导 加压素维持酒精耐受性的能力。一个角色是 作用于大脑V1受体的内源性AVP在维持 耐受性的研究结果支持V1-选择性 单独给予拮抗剂可增加乙醇的损失率 而选择V2的拮抗剂则不能。在 外周，V1加压素受体介导肽诱导 钙动员的改变。AVP的能力 此前有研究表明，维持酒精耐受性取决于 大脑中存在完整的去甲肾上腺素能系统，以及 AVP与神经元定位的V1受体的相互作用可能 改变去甲肾上腺素的释放，从而调节耐受性。 发现了加压素以及催产素和相关的多肽。 阻止或延缓酒精耐受性的发展。两个人 AVP的作用可能通过不同的受体介导。角色 内源性激素在糖尿病的发生和维持中的作用 酒精耐受性也正在通过对 AVP在下丘脑后部的生物合成和释放 垂体和其他组织(垂体前叶、睾丸和间质 细胞培养)。这些研究将调查信使核糖核酸、神经物理蛋白 以及慢性酒精治疗期间的激素水平导致 宽容的养成。初步研究表明， 下丘脑和下丘脑外激素的合成都是 因脱水而增加。其他生理调节剂也是如此 正在研究中。理解组织的作用和作用机制 AVP在耐受性的形成、表达和消散中的作用 乙醇可能导致良性的手段来操纵 对酒精摄入量的耐受性，可能还有。

Arginine vasopressin (AVP) and related peptides, when administered exogenously, prolong the duration of tolerance to ethanol. The similarities between neurohypophyseal peptide effects on tolerance and previously reported effects on memory consolidation supported the hypothesis that these phenomena may share underlying mechanisms. Using peptide agonists that interact selectively with vasopressin V1 and V2 receptors, we have characterized as V1 the receptors in brain that mediate the ability of vasopressin to maintain ethanol tolerance. A role for endogenous AVP, acting at brain V1 receptors, in the maintenance of tolerance was supported by the finding that a V1-selective antagonist, given alone, enhanced the rate of loss of ethanol tolerance, while a V2-selective antagonist did not. In the periphery, V1 vasopressin receptors mediate peptide-induced alterations in calcium mobilization. The ability of AVP to maintain ethanol tolerance was previously shown to depend on the presence of intact noradrenergic systems in brain, and the interaction of AVP with neuronally localized V1 receptors may alter norepinephrine release, and thus modulate tolerance. Vasopressin, as well as oxytocin and related peptides, were found to block or delay the development of ethanol tolerance. The two actions of AVP may be mediated via different receptors. The role of endogenous hormone in the development and maintenance of ethanol tolerance is also being investigated through studies of the biosynthesis and release of AVP in hypothalamus, posterior pituitary and other tissues (anterior pituitary, testis, and Leydig cell cultures). These studies will investigate mRNA, neurophysin and hormone levels during chronic ethanol treatment leading to the development of tolerance. Preliminary studies indicate that both hypothalamic and extrahypothalamic hormone synthesis are increased by dehydration. Other physiological regulators are also being studied. Understanding the role and mechanism of action of AVP in development, expression and dissipation of tolerance to ethanol may lead to benign means for the manipulation of tolerance and, possibly, of ethanol intake.