Vol. 291, Issue 2, 671-679, November 1999

-Adrenoceptors in Canine Mesenteric Artery Are Predominantly 1A Subtype: Pharmacological and Immunochemical Evidence¹

E. E. Daniel , R. Dale Brown , Y. F. Wang , A. M. Low , H. Lu-Chao and C.-Y. Kwan

Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada (E.E.D., Y.F.W., A.M.L., H.L.-C., C.-Y.K.); Smooth Muscle Research Program, McMaster University, Hamilton, Ontario, Canada (E.E.D., R.D.B., Y.F.W., A.M.L., H.L.-C., C.-Y.K.); and Research Service, Edward Hines Jr. Veterans Administration Hospital, Hines, Illinois (R.D.B.)

We wanted to determine which -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-,-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 _1A-adrenoceptors but decreased with concentration. pK_B values (9.6) for Rec 15/2739 (_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 _1A- and _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 EC₅₀ values for PE contractions with pK_B values like those of controls. At 6 nM, phenoxybenzamine 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 _1B-adrenoceptors immunostained muscle of aorta but not mesenteric artery. We conclude that dog mesenteric artery contains _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 _1L-adrenoceptors.