MEDIATION OF NORADRENALINE-INDUCED CONTRACTIONS OF RAT AORTA BY THE ALPHA(1B)-ADRENOCEPTOR SUBTYPE

1 The subtypes of alpha(1)-adrenoceptor mediating contractions to exogenous noradrenaline (NA) in rat aorta have been examined in both biochemical and functional studies. 2 Incubation of rat aortic membranes with the irreversible alpha(1B)-adrenoceptor antagonist, chloroethylclonidine (CEC: 10 mu M) did not change the K-D of [H-3]-prazosin binding in comparison to untreated membranes, but reduced by 88% the total number of binding sites (B-max). 3 Contractions of rat aortic strips to NA after CEC (50 mu M for 30 min) incubation followed by repetitive washing, showed a marked shift in the potency of NA and a partial reduction in the maximum response. The residual contractions to NA after CEC incubation were not affected by prazosin (10 nM). 4 The competitive antagonists prazosin, terazosin, (R)-YM-12617, phentolamine, 5-methylurapidil and spiperone inhibited contractions to NA with estimated pA(2) values of 9.85, 8.54, 9.34, 7.71, 7.64 and 8.41, respectively. 5 The affinity of the same antagonists for the alpha(1A)- and alpha(1B)-adrenoceptors was evaluated by utilizing membranes from rat hippocampus pretreated with CEC, and rat liver, respectively. 5-Methylurapidil and phentolamine were confirmed as selective for the alpha(1A)-adrenoceptors, whereas spiperone was alpha(1B)-selective. 6 A significant correlation was found between the pA(2) values of the alpha(1)-adrenoceptor antagonists tested and their affinity for the alpha(1B)-adrenoceptor subtype, but not for the alpha(1A)-subtype. 7 In conclusion, these findings indicate that in rat aorta most of the contraction is mediated by alpha(1B)-adrenoceptors, and that the potency (pA(2)) of an antagonist in this tissue should be related to its antagonistic effect on this subtype of the alpha(1)-adrenoceptor population.