Correlation between mRNA levels and functional role of alpha1-adrenoceptor subtypes in arteries: evidence of alpha1L as a functional isoform of the alpha1A-adrenoceptor

Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H1923-32. doi: 10.1152/ajpheart.00288.2005. Epub 2005 Jun 10.

Abstract

The mRNA levels for the three alpha1-adrenoceptor subtypes, alpha1A, alpha1B, and alpha1D, were quantified by real-time RT-PCR in arteries from Wistar rats. The alpha1D-adrenoceptor was prominent in both aorta (79.0%) and mesenteric artery (68.7%), alpha1A predominated in tail (61.7%) and small mesenteric artery (73.3%), and both alpha1A- and alpha1D-subtypes were expressed at similar levels in iliac artery. The mRNA levels of the alpha1B-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 alpha1-adrenoceptor antagonists on maximal sustained contraction induced by phenylephrine were constructed from control vessels and vessels pretreated with 100 micromol/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 alpha1D-adrenoceptor antagonist) confirm the relevant role of alpha1D-adrenoceptors in aorta and iliac and proximal mesenteric arteries. The potency of 5-methylurapidil (an alpha1A-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 alpha1A- and alpha1D-adrenoceptors in iliac and distal mesenteric arteries. The low potency of prazosin (pIC50 < 9) as well as the high 5-methylurapidil potency in tail and small mesenteric arteries suggest the main role of alpha1A/alpha1L-adrenoceptors with minor participation of the alpha1D-subtype. The mRNA levels and CEC treatment corroborated this pattern and confirmed that the alpha1L-adrenoceptor could be a functional isoform of the alpha1A-subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects
  • Arteries / metabolism*
  • DNA Primers
  • Dose-Response Relationship, Drug
  • Iliac Artery / drug effects
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Phenylephrine / pharmacology
  • Protein Isoforms
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / biosynthesis*
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • DNA Primers
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Adrenergic, alpha-1
  • Phenylephrine