Sheldon R J, Nunan L, Porreca F
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724.
Eur J Pharmacol. 1988 Feb 9;146(2-3):229-35. doi: 10.1016/0014-2999(88)90297-x.
The mu antagonist property of the kappa agonist U50,488H was studied at the spinal level, using motility of the rat urinary bladder as an endpoint in vivo. Intrathecal (i.th.) administration of the mu agonists [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAGO), [N-MePhe3,D-Pro4]enkephalin (PL017), morphine and normorphine, as well as the delta agonist [D-Pen2,D-Pen5]enkephalin (DPDPE), resulted in an equieffective inhibition of volume-initiated contractions of the urinary bladder. In contrast, i.th. administration of U50,488H, a highly selective kappa agonist, had no effect on bladder motility. Pretreatment of rats with i.th. U50,488H prior to agonist administration, blocked the suppression of spontaneous bladder activity induced by equieffective i.th. does of morphine and normorphine, but failed to alter the inhibitory effect of the mu agonists DAGO and PL017, or that of the delta agonist DPDPE. The finding that U50,488H differentially antagonized the identical bladder effects of several mu agonists suggests the presence of mu receptor subtypes (mu isoreceptors) in the rat spinal cord, which may be involved in the regulation of bladder function.
以大鼠膀胱活动作为体内实验的终点指标，在脊髓水平研究了κ激动剂U50,488H的μ拮抗特性。鞘内注射μ激动剂[D - Ala2，NMePhe4，Gly - ol]脑啡肽（DAGO）、[N - MePhe3，D - Pro4]脑啡肽（PL017）、吗啡和去甲吗啡，以及δ激动剂[D - Pen2，D - Pen5]脑啡肽（DPDPE），均可产生等效的抑制膀胱容量引发收缩的作用。相比之下，鞘内注射高选择性κ激动剂U50,488H对膀胱活动没有影响。在给予激动剂之前，先对大鼠进行鞘内注射U50,488H预处理，可阻断等效剂量鞘内注射吗啡和去甲吗啡所诱导的自发性膀胱活动抑制，但不能改变μ激动剂DAGO和PL017或δ激动剂DPDPE的抑制作用。U50,488H对几种μ激动剂相同的膀胱效应具有差异性拮抗作用，这一发现表明大鼠脊髓中存在μ受体亚型（μ异受体），可能参与膀胱功能的调节。
