Relationship between alpha 1-adrenoceptor density and functional response of rat vas deferens. Studies with phenoxybenzamine.
The relationship between the density of alpha 1-adrenoceptors and the longitudinal contractile response of rat vas deferens was examined by using phenoxybenzamine to irreversibly decrease alpha 1-adrenoceptor density. Receptor density was measured by Scatchard plots of saturation analysis of specific 125I-BE 2254 (125IBE) binding and compared to the potency of alpha-adrenoceptor agonists in causing contraction and the maximum contraction elicited by these agonists. Treatment of isolated vasa deferentia in organ baths with phenoxybenzamine caused a dose-dependent decrease in the density of 125IBE binding sites, the potency of the full agonist phenylephrine in activating contraction, and the maximum contractile response. The percentage of functional receptors remaining after phenoxybenzamine treatment (q value) was calculated from the contraction data and compared to the percentage of 125IBE binding sites remaining. The reduction in the number of functional receptors was much greater than the reduction in the number of 125IBE binding sites at all doses of phenoxybenzamine. Since the magnitude of the contractile response caused by a weak partial agonist should be approximately proportional to the density of functional receptors in the tissue, partial agonists were used as an independent measure of the degree of functional receptor inactivation. Bath application of two different doses of phenoxybenzamine caused a decrease in the maximal contraction caused by the partial agonists clonidine and ephedrine which was similar to the calculated decrease in the q value, but not to the observed decrease in the density of 125IBE binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010627:Phenethylamines / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D044024:Tetralones; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; D010643:Phenoxybenzamine; D010656:Phenylephrine; C010652:BE 2254; D011189:Potassium Chloride