alpha-Adrenoceptors in canine mesenteric artery are predominantly 1A subtype: Pharmacological and immunochemical evidence

We wanted to determine which alpha-adrenoceptor subtypes mediate phenylephr ine (PE) contraction of dog mesenteric artery in vitro. We studied antagoni sms in response to prazosin, 2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4- benzodioxane, 5-methylurapidil, N-[2-(2-cyclopropyl methoxy phenoxy)ethyl]5 -chloro-alpha,alpha-dimethyl-1H-indole-3-ethanamine HCl (RS 17053), 8-3-[4- (2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl)-3-methyl-4-oxo-22-phenyl-4 H-1-benzopyran 2HCl [SB216469 (Rec 15/2739)], BMY 7378, 8-[2-(1,4- benzodio xan-2-ylmethylamino)ethyl]8-azaspirol[4,5]decane-7,9-dione HCl, MDL 72832, and 7-chloro-2-bromo-3,4,5,6-tetrahydro-4-methylfurol[4,3,2-ef]3-benzapine. pK(B) values for prazosin, 5-methylurapidil, MDL 72832, and RS-17053 were consistent with action on alpha(1A)-adrenoceptors but decreased with concen tration. pK(B) values (9.6) for Rec 15/2739 (alpha(1L/1A)-adrenoceptor sele ctive) were constant. Antagonism by BMY 7378, 7-chloro-2-bromo-3,4,5,6-tetr ahydro-4-methylfurol[4,3,2- ef]3-benzapine, and 8-[2-(1,4-benzodioxan-2-ylm ethylamino)ethyl]8-azaspirol[4,5]decane-7,9-dione HCl gave pK(B) values bet ween those expected for alpha(1A)- and alpha(1D)-adrenoceptors. Chloroethyl clonidine (100 mu M) shifted EC50 values for PE rightward and decreased E-m ax values but left large residual responses. After 100 mu M chloroethylclon idine, either BMY 7378 (100 nM) or RS-17053 (300 nM) increased EC50 values for PE contractions with pK(B) values like those of controls. At 6 nM, phen oxybenzamine increased the EC50 values and reduced E-max values; prior Rec 15/2739, but not prior BMY 7378, protected receptors against inactivation. An antibody against the alpha(1B)-adrenoceptors immunostained muscle of aor ta but not mesenteric artery. We conclude that dog mesenteric artery contai ns alpha(1A)-adrenoceptors. Discrepancies among responses expected if only these receptors are present may result from pleiotropic functional effects at this receptor and the presence of alpha(1L)-adrenoceptors.