The effects of yohimbine on presynaptic and postsynaptic events during sympathetic nerve activation in cattle iris: a critique of presynaptic receptor theory.

1 The effects of presynaptic alpha-adrenoceptor blockade on both the efflux of 3H-transmitter and on the magnitude of the effector response were measured simultaneously in a smooth muscle preparation which responds to field stimulation with noradrenergic beta-receptor-mediated relaxation. 2 In the presence of atropine, the circular muscle of cattle iris relaxes in response to noradrenaline and to field stimulation at 2 Hz with 10, 20, 50 and 100 pulses. 3 Yohimbine (3 x 10(-6) M), a potent presynaptic alpha-adrenoceptor antagonist, increased the stimulation-induced efflux of tritium to about 2.0 times control values and, contrary to theory, did so to a similar extent regardless of pulse number and with apparent indifference to the synaptic concentration of transmitter, as confirmed by the varying size of the postsynaptic response. 4 In most cases, yohimbine had no significant effect on the magnitude of the relaxations to nerve stimulation. 5 It is concluded that negative feedback regulation of transmitter release, if it functions at all, and this itself seems doubtful, would not have a substantial impact on the size of the effector response.