Functional evidence of a constitutively active population of alpha(1D)-adrenoceptors in rat aorta.
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.
Gisbert
R
R
Departamento de Farmacología, Facultad de Farmacia, Universitat de València, València, Spain.
Noguera
M A
MA
Ivorra
M D
MD
D'Ocon
P
P
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009122:Muscle Hypertonia / Q000139:chemically induced / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013623:Tail / Q000098:blood supply
C547721:Adra1d protein, rat; D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C053428:BMY 7378; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin