Two distinct adrenoceptor-biophases in the vasculature: one for alpha- and the other for beta-agonists.

Abstract

Strips of two canine vessels with different patterns of sympathetic innervation were used: the mesenteric artery which has an adventitio-medial plexus and the saphenous vein in which nerve terminals are distributed throughout the media. The pD2 of (−)-adrenaline for α-and β-adrenoceptors was determined for both vessels (in the presence of 0.5 μM propranolol and 7 μM phentolamine, respectively; in the latter case the strips were contracted by 0.28 μM prostaglandin F2α) and found to be very similar: 6.96 and 7.01 in the saphenous vein and 6.77 and 6.91 in the mesenteric artery, respectively. The similarity of pD2 for adrenaline acting on α-and β-adrenoceptors in both preparations allowed us to compare the effect of inhibition of neuronal uptake by 12 μM cocaine with that of inhibition of COMT by 50 μM dihydroxy-2-methyl propiophenone (U-0521) on: a) the potency of adrenaline (noradrenaline was used in the saphenous vein only) acting on α-and β-adrenoceptors and b) the time required by the strips to recover 50% in oil (t 50) after contractions or relaxations caused by 0.23 μM adrenaline. In the saphenous vein cocaine increased the potency of both adrenaline and noradrenaline for α-effects more than for β-effects (2.8 times vs. no increase for adrenaline; 7.1 vs. 1.9 times for noradrenaline) and U-0521 increased the potency of both adrenaline and noradrenaline for β-effects more than for α-effects (4.1 vs. 2.6 times for adrenaline; 1.8 times vs. no increase for noradrenaline); regarding the termination of action of adrenaline, cocaine prolonged the t 50 1.6 times after contraction and did not change it after relaxation, whereas U-0521 prolonged the t 50 6.9 times after relaxation and only 1.8 times after contraction. In the mesenteric artery only sensitivity experiments were done. Cocaine increased the potency of adrenaline by a factor of 2.1 for the α-effects while there was no influence on its potency with regard to its β-effects, and U-0521 increased the potency of adrenaline for the β-effects more than for α-effects (3.9 vs. 1.8 times, respectively). These results show that there are two different biophases for sympathomimetic agonists in the vasculature: one for α-adrenoceptors which is more under the influence of the neuronal uptake and one for β-adrenoceptors which is more under the influence of COMT activity. We conclude that α-adrenoceptors are situated close to the nerve endings and β-adrenoceptors close to COMT sites. Since these results do not differ qualitatively in two vessels with different patterns of innervation, we conclude that this asymmetry in the distribution of α-and β-adrenoceptors may be due to either an uneven distribution of cells with only one type of receptors each or due to an uneven distribution of receptors on the same cell.