Vaupel D B, Cone E J, Johnson R E, Su T P
Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, Maryland.
J Pharmacol Exp Ther. 1990 Jan;252(1):225-34.
A diuretic effect of the pentapeptide BW942C [Tyr-D-Met(O)-Gly-pNO2-Phe-Pro-NH2 HCl] was demonstrated in humans and rats; it was characterized pharmacologically using whole animal, isolated tissue and in vitro binding studies. A single 2-mg dose of BW942C increased urine output 5-fold over control values in humans. In Long-Evans rats, BW942C produced a biphasic dose-response curve for urine output with lower doses increasing and higher doses suppressing output. Low doses of naltrexone antagonized the antidiuresis, and high doses antagonized the diuresis produced by BW942C. BW942C was less efficacious in producing diuresis than the full kappa agonists bremazocine and U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate, hydrate). Furthermore, BW942C antagonized the diuretic effects of bremazocine and U50,488H. Rats tolerant to U50,488H-induced diuresis were cross-tolerant to BW942C. In Brattleboro rats, which are unable to synthesize vasopressin, BW942C failed to produce a diuretic effect, demonstrating the necessity of vasopressin for its diuretic response. In the kappa-selective rabbit vas deferens bioassay, BW942C was less efficacious than a full agonist, it was antagonized by naloxone and BW942C in nondepressant doses antagonized a full agonist. In binding studies, BW942C had the highest affinity for mu and delta opioid receptors and an intermediate affinity for kappa opioid receptors. The data suggest that BW942C has the property of a partial kappa opioid agonist in addition to being a mu agonist.
五肽BW942C [酪氨酸-D-蛋氨酸（O）-甘氨酸-对硝基苯丙氨酸-脯氨酸-氨基盐酸盐] 在人和大鼠中均表现出利尿作用；通过整体动物、离体组织和体外结合研究对其进行了药理学特征分析。在人体中，单次给予2毫克BW942C可使尿量比对照值增加5倍。在Long-Evans大鼠中，BW942C对尿量产生双相剂量反应曲线，低剂量增加尿量，高剂量抑制尿量。低剂量的纳曲酮可拮抗抗利尿作用，高剂量则拮抗BW942C产生的利尿作用。与完全κ激动剂布马佐辛和U50,488H（反式-3,4-二氯-N-甲基-N-[2-(1-吡咯烷基)-环己基]-苯乙酰胺甲磺酸盐，水合物）相比，BW942C产生利尿作用的效力较低。此外，BW942C可拮抗布马佐辛和U50,488H的利尿作用。对U50,488H诱导的利尿作用产生耐受的大鼠对BW942C具有交叉耐受性。在无法合成血管加压素的Brattleboro大鼠中，BW942C未能产生利尿作用，这表明血管加压素对其利尿反应是必需的。在κ选择性兔输精管生物测定中，BW942C的效力低于完全激动剂，可被纳洛酮拮抗，且非抑制剂量的BW942C可拮抗完全激动剂。在结合研究中，BW942C对μ和δ阿片受体具有最高亲和力，对κ阿片受体具有中等亲和力。数据表明，BW942C除了是μ激动剂外，还具有部分κ阿片激动剂的特性。
