Alpha 1-adrenoceptor-induced contractility in rat aorta is mediated by the alpha 1D subtype.
Adrenoceptor agonists were used to characterize the alpha 1-adrenoceptor subtype responsible for mediating tension (phasic and tonic combined) in the denuded rat aorta and compared with radioligand binding at alpha 1-adrenoceptor subtypes. The rank order of potency at the rat aorta was the same as that obtained for binding affinity at the rat clonal alpha 1d-adrenoceptor: norepinephrine > epinephrine > cirazoline > phenylephrine > oxymetazoline > A-61603 > methoxamine. Correlation coefficients comparing rat aortic contraction (pD2) to binding (pKi) were 0.09-0.21 for alpha 1A/a receptors, 0.66 for clonal alpha 1b and 0.94 for clonal alpha 1d-adrenoceptors. Correlation coefficients comparing the clonal alpha 1d-adrenoceptor binding affinity to in vitro contractile responses were 0.03 and 0.10 for the rat vas deferens and canine prostate alpha 1A-adrenoceptor responses, respectively, 0.09 for the rat spleen alpha 1B and as noted, 0.94 for the rat aorta. The agreement observed between agonist potency at the rat aorta and affinity for the alpha 1d binding site provide new evidence that the alpha 1D-adrenoceptor subtype is responsible for mediating contractions in the rat aorta.
Buckner
S A
SA
Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Oheim
K W
KW
Morse
P A
PA
Knepper
S M
SM
Hancock
A A
AA
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1