The influence of neuronal uptake upon the relative potencies of agonists acting at prejunctional alpha 2-adrenoceptors in the rat isolated vas deferens.
The effects of inhibition of neuronal uptake upon the potency of the alpha-adrenoceptor antagonist phentolamine and upon the potencies of several agonists which produce inhibition of twitches evoked by field stimulation of the prostatic third of the rat vas deferens are described. In doses producing similar inhibition of the uptake of 3H-noradrenaline, cocaine produced a greater inhibition of the effects of (-)-noradrenaline than did desipramine or diphenhydramine. Cocaine differentially potentiated the effects of the sympathomimetic amines used such that the relative order of agonist potency was changed from xylazine greater than (-)-adrenaline greater than (+)-noradrenaline greater than (-)-metaraminol greater than or equal to (-)-noradrenaline greater than or equal to dopamine, to xylazine greater than (-)-adrenaline greater than (-)-noradrenaline greater than (-)-metaraminol greater than dopamine greater than or equal to (+)-noradrenaline. Prazosin enhanced and yohimbine reduced the twitch inhibition produced by (-)-noradrenaline in the absence of uptake blockers. In contrast, phentolamine had little effect upon the position of the log concentration curve for (-)-noradrenaline except when uptake was inhibited. These experiments demonstrate the marked influence of neuronal uptake upon estimates of the relative potencies of agonists activating alpha 2-adrenoceptors, and upon the estimate of the potency of phentolamine as an antagonist of noradrenaline at these receptors in this densely innervated tissue.
D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D003042:Cocaine; D003891:Desipramine; D009638:Norepinephrine