Potentiation by Smooth Muscle Stimulants of the Hypogastric Nerve — Vas Deferens Preparation from Normal and Castrated Guinea‐Pigs

1 The effects of adrenoceptor agonists and other agonists on the contractile responses of the prostatic and epididymal portions of the rat isolated vas deferens to single pulse field stimulation were investigated. 2 a-Adrenoceptor agonists produced prejunctional c2-mediated inhibition and post-junctional cxl-mediated potentiation of the nerve-induced responses. Guanabenz and xylazine produced mainly inhibitory effects, xylazine being 10 times less potent. Clonidine and oxymetazoline produced inhibition with similar potency to guanabenz but at higher concentrations excitatory effects were present, particularly in the epididymal portion. Phenylephrine produced only potentiation of the nerveinduced response in both portions. Potentiation of nerve-induced responses was a more sensitive and quantitative index of excitation than was direct contraction of the tissue. 3 Isoprenaline and salbutamol both gave fl2-mediated inhibition of the nerve-induced responses in both portions of tissue. At least part of the effect was post-junctional since phenylephrine contractions were inhibited. Isoprenaline also produced a post-junctional ocx-mediated excitation. 4 Noradrenaline produced effects qualitatively similar to those of the other ax-adrenoceptor agonists, inhibition and excitation predominating in the prostatic and epididymal ends respectively. 5 Morphine produced inhibition in the mouse but not in the rat vas deferens. In rat vas, however, enkephalin analogues produced pre-junctional inhibition of responses in both portions which could be partly reversed by naloxone; restoration of the adrenergic component was more complete. Rat anococcygeus showed no equivalent effect. 6 Adenosine 5'-triphosphate (ATP) inhibited nerve-induced responses in each portion with a greater effect on the prostatic portion.

Section: Discussionmentioning

confidence: 88%

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

Macdonald

McGrath

1980

“…Drug concentration (-log M) Figure 4 The effects of the a-adrenoceptor antagon- (Sjostrand & Swedin, 1968;Sjostrand, 1973) of vas deferens without producing contraction but will potentiate the nerve-induced contraction. The other possible explanation for the potentiating effect of these a-adrenoceptor antagonists on the response to a single pulse, namely removal of negative feedback due to spontaneous release of NA, is unlikely since there was no correlation between the order of potency with respect to antagonism of pre-junctional a-receptors.…”

Section: Resultsmentioning

confidence: 99%

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

Brown

McGrath

Summers

1979

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.

“…It is also possible to discount the thesis that SP could exaggerate muscular contraction of the vas by liberating endogenous NA, which might in turn sensitize the tissue via extrajunctional NA receptors (Sjos-C d trand & Swedin, 1968), since the facilitatory effects of SP were not antagonized by phentolamine. Also, the fact that phentolamine potentiated electricallystimulated twitches of the vas, but, unlike SP, abolished the secondary phase of the contraction and accelerated tritium overflow, rules out the likelihood of any interference between SP and prejunctional adrenergic autoreceptors.…”

Section: Discuionmentioning

confidence: 99%

“…Earlier workers have stated that low levels of a variety of agonists, among them SP, are capable of potentiating the nerve-mediated contractions of guinea-pig vas deferens (Sjostrand & Swedin, 1968;Von Euler & Hedqvist, 1974). The exquisite sensitivity of this preparation to small doses of SP prompted Von Euler & Hedqvist (1974) to conjecture that,subspasmogenic doses of the peptide may depolarize the muscle membrane subliminally and thereby raise its senstivity to all subsequent forms of depolarizing stimuli (cf.…”

Section: Discuionmentioning

confidence: 99%

“…Birmingham & Wilson (1963) devised a simple method of transmural stimulation for triggering this rich intramural network of short postganglionic noradrenergic nerve fibres, thereby contracting the vas, since which time the pharmacology of this preparation has been extensively studied. One feature of the nerve-mediated contractions pf guinea-pig vas deferens is their unusual susceptibility to potentiation by exceptionally small concentrations of a wide variety of agonists, among them substance P (SP; Sjostrand & Swedin, 1968;Von Euler & Hedqvist, 1974).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Potentiation by Substance P of Contractions of the Isolated Vas Deferens of the Mouse Elicited by Electric Field Stimulation and by Drugs

Blackwell¹,

James²,

Starr³

1978

1 Isolated vasa deferentia from the mouse were opened longitudinally and suspended in Krebs solution at 37°C in an organ bath. Contractions of the muscle were elicited by electric field stimulation, noradrenaline (10-6 M) and acetylcholine (10-6 M). Continued transmural stimulation evoked a biphasic response comprising a rapid twitch followed about 10s later by a smaller, sustained rise in muscle tone. 2 The amplitudes of nerve-mediated and drug-induced responses were considerably potentiated by substance P-(SP) in the dose range 10-12 to 10-M. Higher concentrations of SP were directly spasmogenic. The sensitizing property of SP was dose-dependent and was usually well maintained, but always disappeared quickly on washing the preparation. In some experiments SP facilitated the twitch, but not the subsequent phase of the electrically-induced contraction or the response to externally applied noradrenaline. 3 Phentolamine (10-6 M) failed to block this effect of SP, but itself potentiated the nerve-mediated twitch, and completely abolished the sustained secondary contraction. 4 Desmethylimipramine (10-6 M) enhanced the delayed contraction but not the immediate contraction. 5 The uptake of tritiated noradrenaline (3 x lo-M) by vasa was inhibited by desmethylimipramine (10-6M) and increased by nialamide (3 x 10-5M), but was not modified by SP (10-6M). 6 Nerve-mediated release of accumulated radioactivity was accelerated by phentolamine, but not by SP or desmethylimipramine. 7 These findings suggest that SP sensitizes the muscle cells to depolarizing stimuli but that it has no facilitatory effect on sympathetic neural elements.