Tsushima H, Mori M, Matsuda T
Department of Pharmacology, Nagoya City University Medical School, Japan.
Jpn J Pharmacol. 1997 May;74(1):45-9. doi: 10.1254/jjp.74.45.
We have investigated opioid mechanisms concerning regulation of urine production in the hypothalamic supraoptic nucleus (SON). In this study, the effect of [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), a potent selective mu-opioid agonist, microinjected into the SON of anesthetized hydrated rats, on the urine outflow rate was examined. DAMGO caused a dose-dependent decrease in the urine outflow rate with no significant changes in blood pressure nor heart rate. The ED50 value for the antidiuresis was calculated to be 0.055 nmol from the dose-response curve. The antidiuresis elicited by DAMGO (0.1 nmol) was partially inhibited by intra-SON pre-injection of naloxone (3 nmol), a relatively mu-selective opioid antagonist, and timolol (100 nmol), a beta-adrenoceptor antagonist, but not by intra-SON pre-injection of phenoxybenzamine (20 nmol), an alpha-adrenoceptor antagonist, nor atropine (300 nmol), a muscarinic antagonist. Intravenous injection of d(CH2)5-D-Tyr(Et)VAVP (16.7 micrograms), a vasopressin receptor antagonist, did not influence the DAMGO-induced antidiuresis. These findings suggest that antidiuresis mediated through mu-opioid receptors in the SON involves beta-adrenoceptors in the nuclei, but does not involve an increase in vasopressin release.
我们研究了阿片类物质在下丘脑视上核（SON）中调节尿液生成的机制。在本研究中，检测了将强效选择性μ-阿片受体激动剂[D-丙氨酸2，N-甲基苯丙氨酸4，甘氨酸5-醇]-脑啡肽（DAMGO）微量注射到麻醉的水合大鼠的SON中对尿流率的影响。DAMGO导致尿流率呈剂量依赖性下降，而血压和心率无显著变化。根据剂量-反应曲线计算，抗利尿作用的ED50值为0.055 nmol。DAMGO（0.1 nmol）引起的抗利尿作用被SON内预先注射相对选择性的μ-阿片受体拮抗剂纳洛酮（3 nmol）和β-肾上腺素能受体拮抗剂噻吗洛尔（100 nmol）部分抑制，但未被SON内预先注射α-肾上腺素能受体拮抗剂酚苄明（20 nmol）或毒蕈碱拮抗剂阿托品（300 nmol）抑制。静脉注射血管加压素受体拮抗剂d(CH2)5-D-Tyr(Et)VAVP（16.7微克）不影响DAMGO诱导的抗利尿作用。这些发现表明，SON中通过μ-阿片受体介导的抗利尿作用涉及核内的β-肾上腺素能受体，但不涉及血管加压素释放增加。
