Tsushima H, Mori M, Matsuda T
Department of Pharmacology, Nagoya City University Medical School, Japan.
Jpn J Pharmacol. 1987 Dec;45(4):449-57. doi: 10.1254/jjp.45.449.
Effects of morphine microinjected into the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, which contain neurons producing and releasing antidiuretic hormone (vasopressin), on the outflow and the osmotic pressure of urine and other visceral functions were investigated in a rat which was loaded with water and anesthetized with ethanol. The opioid drug, having predominantly mu-agonist activity, when microinjected into the SON or PVN induced potent antidiuretic effects in dose-dependent and time-dependent manners with no significant effects on the other visceral functions. The approx. ED50 values for morphine were 19 and 9 nmol when it was microinjected into the SON and PVN, respectively. The antidiuretic effects showed slow onset and long duration, with a minimal outflow at approx. 50 min after microinjection and a return to approx. 50% of the initial control value by 1.5 hr. The morphine-induced effects were inhibited by pretreatment with naloxone or atropine, but not inhibited by pretreatment with alpha- or beta-adrenoceptor antagonists, suggesting that the antidiuretic effects were mediated through an opioid receptor having low sensitivity to naloxone and also possibly mediated through a muscarinic receptor which was stimulated probably by the ACh released by morphine.
将吗啡微量注射到下丘脑视上核（SON）和室旁核（PVN）中，这两个核团含有产生和释放抗利尿激素（血管加压素）的神经元，研究其对水负荷并用乙醇麻醉的大鼠尿液排出量、渗透压及其他内脏功能的影响。这种主要具有μ-激动剂活性的阿片类药物，微量注射到SON或PVN中时，会以剂量依赖性和时间依赖性方式诱导强烈的抗利尿作用，而对其他内脏功能无显著影响。当吗啡微量注射到SON和PVN中时，其近似ED50值分别为19和9 nmol。抗利尿作用起效缓慢且持续时间长，微量注射后约50分钟尿量流出最少，到1.5小时时恢复到初始对照值的约50%。吗啡诱导的作用可被纳洛酮或阿托品预处理抑制，但不能被α-或β-肾上腺素能受体拮抗剂预处理抑制，这表明抗利尿作用是通过对纳洛酮敏感性低的阿片受体介导的，也可能是通过可能由吗啡释放的乙酰胆碱刺激的毒蕈碱受体介导的。
