The EFFECTS OF Α‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON RESPONSES OF TRANSMURALLY STIMULATED PROSTATIC AND EPIDIDYMAL PORTIONS OF THE ISOLATED VAS DEFERENS OF THE RAT

Abstract

1 The effects of a-adrenoceptor agonists and antagonists on contractile responses of transmurally stimulated prostatic and epididymal portions of the rat isolated vas deferens were examined. 2 Responses to single stimuli consisted of two phases, the first predominant in the prostatic and the second in the epididymal portion. The first phase was resistant to a-adrenoceptor antagonists but the second was reduced in a dose-related manner in the order of potency prazosin > azapetine > phentolamine > labetalol > yohimbine. 3 Both phases of the response to a single stimulus were reduced by clonidine but only the first could be reliably restored by yohimbine. 4 Trains of transmural stimuli produced biphasic. responses, an early rapid component predominant in the prostatic and a slower secondary component predominant in the epididymal portion. The effects of a-adrenoceptor antagonists on these responses were complex. Prazosin produced the most straightforward inhibition of responses with relative resistance of the early rapid component. Only yohimbine and phentolamine produced increases in responses which could be pre-junctional in origin. 5 The a-adrenoceptor agonists, oxymetazoline and clonidine, reduced while phenylephrine increased responses to trains of stimuli. 6 These results are discussed in relation to the nature of the innervation of rat vas deferens and the usefulness of the preparation in pharmacological tests for activity at a-adrenoceptors.

The Distribution of Adrenoceptors and Other Drug Receptors Between the Two Ends of the Rat Vas Deferens as Revealed by Selective Agonists and Antagonists

“…With every agonist the potentiation at 1500 ms could be reduced by prazosin (6 x 10-6 M) or yohimbine (6 x 10-6 M) leaving only a small, monophasic response qualitatively similar to that which would have been produced after the antagonist alone (Brown et al, 1979) e.g. epididymal response, 1500 ms, as a percent of control; after clonidine (10-7 M) 643 + 80; after clonidine and yohimbine (6 x 10-6 M) 126 + 21 (n = 6, paired t test, P < 0.0001); this indicates that some excitatory effect remains, i.e.…”

“…In the epididymal end, contractile responses to nerve stimulation are mainly adrenergic since they are reduced by reserpine pretreatment or acute administration of post-junctional a-adrenoceptor antagonists and are potentiated by blockers of the neuronal uptake of noradrenaline. In contrast, the main part of the response in the prostatic end is resistant to these types of drugs (Anton, Duncan & McGrath, 1977;McGrath, 1978;Brown, McGrath & Summers, 1979).…”

“…Field stimulation of the intramural nerve fibres was applied only as single pulses to avoid eliciting endogenous inhibition by noradrenaline acting at prejunctional 22-adrenoceptors (Brown et al, 1979). Earlier work on whole vasa had demonstrated that these prejunctional receptors could be activated by the agonists clonidine, oxymetazoline and xylazine (but not by phenylephrine) and could be antagonized by yohimbine (but not by prazosin) (Drew, 1977;Doxey, Smith & Walker, 1977).…”

Separation of adrenergic and non‐adrenergic contractions to field stimulation in the rat vas deferens

“…At higher concentrations all a-antagonists which have been tested produce a post-junctional excitatory effect which increases the responses to single stimuli and eventually leads to spontaneous contraction of the vasa (Brown, McGrath & Summers, 1979). This can give a false impression of prejunctional antagonism.…”

“…Although the greater part of the adrenergic nerveinduced contraction occurs within the first few seconds of a train and is nifedipine-resistant, there is a small, maintained, ol, adrenergic component throughout the duration of the train, which is responsible for the well-documented but small reduction of the 'secondary' response to trains by a,-blockade (Swedin, 1971;Anton et al, 1977;Brown et al, 1979). This can be regarded as a third component (III) of nerve transmission and is the 'second' which is adrenergic.…”