Abstract

We wanted to determine which α-adrenoceptor subtypes mediate phenylephrine (PE) contraction of dog mesenteric artery in vitro. We studied antagonisms in response to prazosin, 2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane, 5-methylurapidil, N-[2-(2-cyclopropyl methoxy phenoxy)ethyl]5-chloro-α,α-dimethyl-1H-indole-3-ethanamine HCl (RS 17053), 8–3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl)-3-methyl-4-oxo-22-phenyl-4H-1-benzopyran 2HCl [SB216469 (Rec 15/2739)], BMY 7378, 8-[2-(1,4-benzodioxan-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 α_1A-adrenoceptors but decreased with concentration. pK_B values (9.6) for Rec 15/2739 (α_1L/1A-adrenoceptor selective) were constant. Antagonism by BMY 7378, 7-chloro-2-bromo-3,4,5,6-tetrahydro-4-methylfurol[4,3,2-ef]3-benzapine, and 8-[2-(1,4-benzodioxan-2-ylmethylamino)ethyl]8-azaspirol[4,5]decane-7,9-dione HCl gave pK_B values between those expected for α_1A- and α_1D-adrenoceptors. Chloroethylclonidine (100 μM) shifted EC₅₀ values for PE rightward and decreased E_max values but left large residual responses. After 100 μM chloroethylclonidine, either BMY 7378 (100 nM) or RS-17053 (300 nM) increased EC₅₀values for PE contractions with pK_B values like those of controls. At 6 nM, phenoxybenzamine increased the EC₅₀ values and reduced E_maxvalues; prior Rec 15/2739, but not prior BMY 7378, protected receptors against inactivation. An antibody against the α_1B-adrenoceptors immunostained muscle of aorta but not mesenteric artery. We conclude that dog mesenteric artery contains α_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 α_1L-adrenoceptors.