U50,488H differentially antagonizes the bladder effects of μ agonists at spinal sites

The μ antagonist property of the gk 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 μ agonists [D-Ala², NMePhe⁴, Glyol]enkephalin (DAGO), [N-MePhe³,D-Pro⁴]enkephalin (PL017), morphine and normorphine, as well as the gd 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 κ 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. doses of morphine and normorphine, but failed to alter the inhibitory effect of the μ agonists DAGO and PL017, or that of the gd agonist DPDPE. The finding that U50,488H differentially antagonized the identical bladder effects of several μ agonists suggests the presence of μ receptor subtypes (μ isoreceptors) in the rat spinal cord, which may be involved in the regulation of bladder function.