The effects of prazosin, phentolamine and phenoxybenzamine on inhibitory alpha-adrenoceptors in the guniea-pig isolated ileum.

1 The relaxant effect of noradrenaline on strips of guinea-pig isolated terminal ileum was blocked by pretreatment with prazosin, phentolamine, yohimbine and phenoxybenzamine. 2 The presence of a very high concentration of noradrenaline (50 micrometers) during exposure to the blocking agent protected against the blocking effect of the drugs. 3 Yohimbine, prazosin and phentolamine partially protected against irreversible blockade by phenoxybenzamine. 4 Spontaneous release of acetylcholine in the unstimulated ileum was blocked by noradrenaline (0.05-5.9 micrometers) this effect of noradrenaline was antagonized by phentolamine (0.13-26 micrometers) and yohimbine (0.051-0.51 micrometers) but not prazosin (0.53-5.3 micrometers) or phenoxybenzamine (4.2-42 nm). All four antagonists reversed the noradrenaline-induced relaxation of the ileum. 5 Acetylcholine output in the transmurally stimulated ileum was inhibited by noradrenaline. This effect of noradrenaline was antagonized by phentolamine and yohimbine but not by prazosin or phenoxybenzamine. The first two antagonists blocked the noradrenaline-induced inhibition of evoked twitches of the ileum while the last two had no effect. 6 The results show (a) that prazosin has no effect on presynaptic alpha-adrenoceptor located on cholinergic nerve endings in the guinea-pig ileum and (b) that prazosin, phentolamine and phenoxybenzamine act on the same subgroup of postsynaptic alpha-adrenoceptors on the smooth muscle of the guniea-pig ileum.