Alpha-adrenoceptors in canine mesenteric artery are predominantly 1A subtype: pharmacological and immunochemical evidence.
We wanted to determine which alpha-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-alpha,alpha-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 alpha(1A)-adrenoceptors but decreased with concentration. pK(B) values (9.6) for Rec 15/2739 (alpha(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]de cane-7,9-dione HCl gave pK(B) values between those expected for alpha(1A)- and alpha(1D)-adrenoceptors. Chloroethylclonidine (100 microM) shifted EC(50) values for PE rightward and decreased E(max) values but left large residual responses. After 100 microM chloroethylclonidine, either BMY 7378 (100 nM) or RS-17053 (300 nM) increased EC(50) values for PE contractions with pK(B) values like those of controls. At 6 nM, phenoxybenzamine increased the EC(50) 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 aorta but not mesenteric artery. We conclude that dog mesenteric artery contains 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.
Daniel
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Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. daniele@fhs.csu.McMaster.Ca
Brown
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RD
Wang
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YF
Low
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AM
Lu-Chao
H
H
Kwan
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CY
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D000906:Antibodies; D001011:Aorta / Q000276:immunology; D004396:Coloring Agents; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000276:immunology; D010656:Phenylephrine / Q000494:pharmacology*; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000906:Antibodies; D004396:Coloring Agents; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine