The effects of clonidine, guanfacine and phenylephrine on the excitatory and inhibitory responses of the rat anococcygeus muscle.

Abstract

The effects of clonidine, guanfacine and phenylephrine on twitch responses and the basal tone of the rat anococcygeus muscle were investigated. Clonidine (10(-9)-3 x 10(-8) M) and guanfacine (10(-9)-10(-7) M) inhibited the twitch responses with the same potency, whereas phenylephrine (10(-9)-10(-7) M) was found ineffective. The inhibitory effect of clonidine and guanfacine was antagonized by yohimbine. Higher concentrations of clonidine and guanfacine increased the muscle tone and elicited inhibitory responses during field stimulation. Phenylephrine at concentrations greater than 10(-7) M also increased the muscle tone but induced biphasic responses. Clonidine (10(-7)-3 x 10(-5) M), guanfacine (3 x 10(-7)-3 x 10(-5) M) and phenylephrine (3 x 10(-7)-10(-5) M) caused concentration-dependent increases in the basal tone. The order of potency of these agonists in increasing the basal tone was clonidine > guanfacine > phenylephrine. Both yohimbine (10(-8)-10(-5) M) and prazosin (10(-9)-10(-7) M) antagonized these tonic contractions. Prazosin was found to be 39-, 122- and 83-fold more potent than yohimbine in antagonizing clonidine, guanfacine and phenylephrine-induced tonic contractions, respectively. Clonidine and guanfacine inhibited twitch responses through stimulation of presynaptic alpha-2 adrenoceptors. Postsynaptic alpha-1 adrenoceptors seem responsible for the contractile effects of clonidine, guanfacine and phenylephrine in the rat anococcygeus muscle.