Effects of U-50 488H, a kappa-agonist, on action potentials of isolated ventricular papillary muscle of guinea pigs.
Trans(+-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzeneacetamide-methanesulfonate-hydrate (U-50 488H), a specific kappa-agonist, at 1-10 mumol.L-1 caused concentration-dependent reductions in the action potential duration at 50% and 90% of repolarization (APD50 and APD90) without modifying the resting potential (RP), the action potential amplitude (APA) and the maximal upstroke velocity (Vmax). The effects were attenuated by (-)-(1R,5R,9R)-5,9-diethyl-2-(3-furylmethyl)-2L-hydroxy-6,7-benzomorphan (M(r) 2266 BS, 1 mumol.L-1), a specific kappa-antagonist which itself had no effect on the action potentials of the ventricular papillary muscle of guinea pigs, indicating that U-50 488H at 1-10 mumol.L-1 acts via specific cardiac kappa-receptors. At 100 mumol.L-1, U-50 488H not only shortened APD50 and APD90, but also reduced RP, APA, and Vmax, which were not attenuated by Mr 2266 BS (1 mumol.L-1) suggesting that the effects of U-50 488H at 100 mumol.L-1 were probably nonspecific.
Sheng
J Z
JZ
Department of Physiology, Faculty of Medicine, University of Hong Kong.
Dong
H
H
Wong
T M
TM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology*
D001575:Benzomorphans; D011759:Pyrrolidines; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer