The Effects of Release and Depletion of Endogenous Noradrenaline on the Transmission of Impulses in the Mouse Vas Deferens

Abstract

1 The effects of endogenous noradrenaline released by tyramine and the influence of depletion of the tissue noradrenaline with reserpine and/or oa-methyl-p-tyrosine on the twitch responses of the field-stimulated mouse vas deferens have been studied.2 Tyramine (10-40 gM) inhibited the twitch responses to field stimulation and failed to produce a contraction. The inhibition decreased as the rate of stimulation increased.3 The inhibition produced by tyramine was antagonized by cocaine (10 PM) and by yohimbine (10 nM), which indicated that it was produced by released noradrenaline acting on presynaptic a-adrenoceptors. 4 Depletion of the tissue noradrenaline by 39% by blockade of the synthesis of noradrenaline with a-methyl-p-tyrosine, was without effect on the twitch response but it reduced the inhibitory effect of tyramine. 5 Depletion of the tissue noradrenaline by 96.5% with reserpine alone and by 99.4%, with a combination of reserpine and ax-methyl-p-tyrosine, reduced the twitch responses by approximately 66% and virtually abolished the inhibition produced by tyramine. It also increased the rate of decline of the responses when the tissue was continuously stimulated. The remaining twitch was not antagonized by phenoxybenzamine (15 gM).6 Residual twitches were bigger in tissues depleted by 99.4% than in those depleted by only 96.5%. This difference was eliminated in the presence of yohimbine (128 nM). 7 It is concluded that inhibition of the twitch responses by tyramine is produced by stimulation of presynaptic a-adrenoceptors and that the twitch response is associated with stimulation of the sympathetic neurone, but that it is not mediated by postsynaptic a-adrenoceptors.

An Electrophysiological Analysis of the Effects of Morphine on the Calcium Dependence of Neuromuscular Transmission in the Mouse Vas Deferens

“…as well as the motor response and the effects of atropine on the motor response are themselves blocked by desmethylimipramine (Jones & Spriggs, 1975b). Although the motor response of the vas deferens during short trains of impulses is reduced only 66% following a 97% reduction of the NA levels with reserpine (Marshall, Nasmyth & Shepperson, 1978), this may be due to reserpine reversing the normal depression in ej.p. amplitude which occurs during a high-frequency train to facilitation (see Figure 2 in Bennett & Middleton, 1975a).…”

Effects of Metoclopramide and Isoprenaline in the Rat Vas Deferens; Interactions With Α‐adrenoceptors

“…The rapid decline in developed tension following repeated field stimulation (Figure 4) indicates that an endogenous inhibitory mechanism was activated during these experiments. Marshall, Nasmyth & Shepperson (1978) have shown, in the mouse vas deferens, that the inhibitory effects of tyramine on responses to field stimulation are mediated by displaced noradrenaline acting on presynaptic a-adrenoceptors. Thus, the ability of metoclopramide to antagonize the inhibitory effects of tyramine is evidence that metoclopramide may antagonize endogenously-released noradrenaline.…”

An electrophysiological study of presynaptic α‐adrenoceptors in the vas deferens of the mouse

“…It seems possible, therefore, that extrajunctional adrenoceptors (Hotta, 1969) of the a1-type were reached by the amine. It has been known for some time that contractions (Ambache & Zar, 1971;Jones & Spriggs, 1975) or depolarizations (Burnstock & Holman, 1962;1964;Holman, 1967) (Jenkins et al, 1977;Marshall et al, 1978b; for further possible explanations see Furness, 1974 tant to high concentrations of the dopamine receptor antagonist, haloperidol. The reduction of noradrenaline-evoked depolarizations caused by haloperidol is probably due to an a-antagonist effect of this compound.…”

“…The motor transmitter of the postganglionic sympathetic neurones of the mouse vas deferens is noradrenaline (Farnebo & Mahmfors, 1971;Henderson, Hughes & Kosterlitz, 1972;Bennett & Middleton, 1975a;Jones & Spriggs, 1975), although some of the receptors for the transmitter at the smooth muscle cells may differ from a-and P-adrenoceptors, and the contribution of a second, unknown motor transmitter has not been entirely ruled out (Jenkins, Marshall & Nasmyth, 1977;Marshall, Nasmyth & Shepperson, 1978b). As in many other noradrenergically innervated tissues, the release of the motor transmitter is inhibited by activation of presynaptic aadrenoceptors.…”