Evidence for the existence of distinct biophases for alpha- and beta-adrenoceptors in the vascular tissue.

In dog mesenteric artery and saphenous vein strips, the inhibition of neuronal uptake by cocaine increased the potency of exogenous adrenaline for alpha-effects and did not change its potency for beta-effects, whereas inhibition of catechol-O-methyltransferase (COMT) by U-0521 enhanced the beta-effects more than the alpha-ones. On the other hand, cocaine prolonged the duration of adrenaline-induced contraction more than it prolonged the adrenaline-induced relaxation, while U-0521 prolonged the duration of the relaxation much more than that of the contraction. Cocaine and U-0521 also caused differential influences on alpha- and beta-effects caused by endogenous adrenaline, i.e., on alpha- and beta-effects caused by electrical stimulation of strips previously preloaded with adrenaline. It was also observed that the time elapsing between the beginning of the electrical stimulation and the onset of the response (latency) is longer for beta- than for alpha-responses when both are evoked by electrical stimulation. Furthermore, in these strips, alpha-adrenoceptor blocking agents more easily antagonized the contractions caused by exogenous adrenaline than contractions caused by electrical stimulation, whereas propranolol antagonized beta-responses caused by exogenous adrenaline as easily as beta-responses caused by electrical stimulation. It is concluded that there is a biophase for alpha-adrenoceptors, which is under greater influence of neuronal uptake, and another for beta-adrenoceptors, which is under greater influence of COMT activity.