Correlation between mRNA levels and functional role of α1-adrenoceptor subtypes in arteries:: evidence of α1L as a functional isoform of the α1A-adrenoceptor

The mRNA levels for the three alpha(1)-adrenoceptor subtypes, alpha(1A), alpha(1B), and alpha(1D), were quantified by real-time RT-PCR in arteries from Wistar rats. The alpha(1D)-adrenoceptor was prominent in both aorta (79.0%) and mesenteric artery (68.7%), alpha(1A) predominated in tail (61.7%) and small mesenteric artery (73.3%), and both alpha(1A)- and alpha(1D)- subtypes were expressed at similar levels in iliac artery. The mRNA levels of the alpha 1B-subtype were a minority in all vessels (1.7-11.1%). Concentration-response curves of contraction in response to phenylephrine or relaxation in response to alpha(1)-adrenoceptor antagonists on maximal sustained contraction induced by phenylephrine were constructed from control vessels and vessels pretreated with 100 mu mol/l chloroethylclonidine (CEC) for 30 min. The significant decrease in the phenylephrine potency observed after CEC treatment together with the inhibitory potency displayed by 8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]8- azaspiro ( 4,5) decane-7-dionedihydrochloride} (BMY-7378, an alpha(1D)-adrenoceptor antagonist) confirm the relevant role of alpha(1D)-adrenoceptors in aorta and iliac and proximal mesenteric arteries. The potency of 5-methylurapidil (an alpha(1A)-adrenoceptor antagonist) and the changes in the potency of both BMY-7378 and 5-methylurapidil after CEC treatment provided evidence of a mixed population of alpha(1A)- and alpha(1D)-adrenoceptors in iliac and distal mesenteric arteries. The low potency of prazosin (pIC(50) < 9) as well as the high 5-methylurapidil potency in tail and small mesenteric arteries suggest the main role of alpha(1A)/alpha(1L)-adrenoceptors with minor participation of the alpha(1D)-subtype. The mRNA levels and CEC treatment corroborated this pattern and confirmed that the alpha(1L)-adrenoceptor could be a functional isoform of the alpha(1A)-subtype.