Functional evidence of a constitutively active population of alpha(1D)-adrenoceptors in rat aorta

J Pharmacol Exp Ther. 2000 Nov;295(2):810-7.

Abstract

After depletion of intracellular calcium stores sensitive to noradrenaline, a spontaneous increase in the resting tone (IRT) when incubated in Ca(2+)-containing solution was observed in isolated rat aorta, but not in tail artery. This IRT does not depend on agonist activation of alpha(1)-adrenoceptors but it is inhibited by prazosin. A close relationship was found between the inhibitory potencies of prazosin (pIC(50) = 9.833), BMY 7378 (pIC(50) = 8.924), and 5-methylurapidil (pIC(50) = 7.883) against IRT and their affinities for cloned alpha(1D)-adrenoceptors. Chloroethylclonidine (100 micromol. l(-1)) did not inhibit the IRT. After depletion of internal calcium stores by noradrenaline in absence of the agonist, loading in Ca(2+)-containing solution also brings about an increase in the inositol phosphate (IP) levels in rat aorta (not seen in tail artery) that is inhibited by prazosin (1 micromol. l(-1)), BMY 7378 (10 micromol. l(-1)), and 5-methylurapidil (10 micromol. l(-1)), thus confirming the results obtained in contractile studies. Chloroethylclonidine (100 micromol. l(-1)) did not inhibit this IP accumulation. The fact that the IRT and the IP accumulation related to it can be selectively inhibited by different alpha(1)-adrenoceptor antagonists suggests the existence of a population of alpha(1D)-adrenoceptors that show constitutive activity in rat aorta, not in tail artery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / physiology*
  • Arteries / drug effects
  • Arteries / metabolism
  • Arteries / physiology
  • Calcium / metabolism
  • Calcium / pharmacology
  • Female
  • In Vitro Techniques
  • Inositol Phosphates / metabolism
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle Hypertonia / chemically induced
  • Muscle Hypertonia / metabolism
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiology
  • Norepinephrine / pharmacology
  • Piperazines / pharmacology
  • Prazosin / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Tail / blood supply

Substances

  • Adra1d protein, rat
  • Adrenergic alpha-Antagonists
  • Inositol Phosphates
  • Piperazines
  • Receptors, Adrenergic, alpha-1
  • BMY 7378
  • Calcium
  • Norepinephrine
  • Prazosin