Effect of alpha-adrenergic agonists and antagonists on neurotransmission in the rat anococcygeus muscle.

The isolated rat anococcygeus muscle was found to be a sensitive preparation for the study of the pre- and postsynaptic actions of α-adrenergic agonists and antagonists. The pre- and postsynaptic actions of α-agonists were characterized by comparing the order of potency (1) for directly contracting smooth muscle, (2) for inhibiting the field-stimulated release of tritium (³H) or ³H-norepinephrine, following labelling of adrenergic stores with ³H-NE and (3) for inhibiting twitch contractions elicited by field-stimulation. Clonidine, oxymetazoline tetrahydrozoline and naphazoline, listed in their order of potency, inhibited field-stimulated ³H-release and twitch contractions. With the exception of clonidine, a clear separation of pre- and postsynaptic α-mediated effects was not achieved with the other imidazolines tested. In contrast, methoxamine and phenylephrine did not inhibit twitch response or ³H-release, but did cause a direct contraction of the smooth muscle. The α-antagonists, phentolamine, yohimbine and phenoxybenzamine increased the stimulated release of ³H in a concentration dependent manner. At 10^?7 M, yohimbine preferentially blocked presynaptic α-receptors. Phentolamine was the most potent antagonist at pre- or postsynaptic α-receptors, but like phenoxybenzamine showed no selectivity for pre- or postsynaptic α-receptors. The percent inhibition of neurotransmitter released produced by the α-agonists was found to be inversely proportional to the train lenght, frequency of stimulation and extracellular calcium. Because of the differential effects of α-agonists at pre- and postsynaptic sites, α-receptors on nerve varicosities may have different structural requirements for blockade and activation than the α-receptors on smooth muscle.