The effect of prazosin on the guinea-pig ileum

1 The alpha-adrenoceptor blocking activity of prazosin was compared with that of phentolamine, yohimbine and phenoxybenzamine in the guinea-pig isolated ileum. 2 Phentolamine (2.56 X 10(-8) to 2.56 X 10(-6) M) and yohimbine (5.12 X 10(-8) to 5.12 X 10(-6) M) antagonized the sympathetic inhibition of twitches induced by transmural stimulation, whereas prazosin (5.28 X 10(-8) to 5.28 X 10(-6) M) and phenoxybenzamine (4.2 X 10(-9) to 4.2 X 10(-7) M) had no effect. 3 Phentolamine, yohimbine, prazosin and phenoxybenzamine antagonized the relaxant response of the ileum to periarterial nerve stimulation and to exogenous noradrenaline in the absence of transmural stimulation. 4 The pA2 value for phentolamine against noradrenaline in the transmurally-stimulated gut (presynaptic alpha-adrenoceptor site; 8.17 +/- 0.04) was significantly different from that in the non-stimulated gut (postsynaptic alpha-adrenoceptor site; 6.88 +/- 0.12). 5 Phentolamine and prazosin probably block noradrenaline responses at the same alpha-adrenoceptor site on the postsynaptic membrane.