Characterization of alpha1-adrenoceptor subtypes in facilitation of rat spinal motoneuron activity

Abstract

The subtypes of alpha1-adrenoceptor mediating facilitation of alpha-motoneuron activity in adult rat spinal cord were examined. The potencies of agonists and antagonists were compared, using extracellular single unit recordings made in spinal cord slices isolated from adult rats. Catecholamines (epinephrine, norepinephrine), phenylethylamines (phenylephrine, methoxamine) and imidazolines (clonidine, oxymetazoline, St587 (2-(2-chloro-5-trifluoromethyl-phenylimino)-imidazoline)) enhanced motoneuron activity. Catecholamines and phenylethylamines elicited maximal responses but imidazolines elicited submaximal responses. The potencies of the agonists were similar to their affinities for alpha1A-adrenoceptors. The alpha1A-adrenoceptor agonist SDZ NVI 085 ((-)-(4aR,10aR)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9-methylthio-2H-naphth[2,3b]-1,4-oxazine) behaved as a partial agonist with a maximal response of about 75% and this response was not inhibited by chloroethylclonidine. Pretreatment with chloroethylclonidine produced a rightward shift of the phenylephrine response curve but caused little reduction in the maximal response. Prazosin, 5-methyl-urapidil, WB4101 (2-([2,6-dimethoxyphenoxyethyl] aminomethyl)-1,4-benzodioxane) and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8azaspiro[4.5]decane-7,9-dione dihydrochloride) concentration dependently inhibited the facilitation of alpha-motoneuron activity produced by phenylephrine. The order of inhibitory potency was similar to that for their alpha1A-adrenoceptor binding site affinity. Therefore, it seems that alpha1A-adrenoceptors may be functionally predominant in the facilitation of rat spinal motoneuron activity.