Inhibition of post‐ganglionic motor transmission in vas deferens by indirectly acting sympathomimetic drugs

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.

Section: Dicussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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

Marshall

Nasmyth

Shepperson

1978

“…The fact that clonidine did not cause a contraction of the vas deferens and that the presynaptic inhibition was antagonized by phentolamine despite the presence of a postsynaptic aadrenoceptor (Gillespie & McGrath, 1975) reflected the unusual nature of the motor response in the vas deferens. The role of noradrenaline in the transmission process of the vas deferens has been questioned by Ambache & Zar (1971) and Ambache, Dunk, Verney & Zar, (1972). If however, as suggested by Gillespie & McGrath (1975), noradrenaline is the transmitter a possible explanation could be that hypogastric nerves have a very high population of presynaptic aadrenoceptors in comparison with other sympathetic nerves or that the postsynaptic a-adrenoceptor is less accessible to exogenously administered agonists and antagonists.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Clonidine on Responses to Sympathetic Nerve Stimulation in the Pithed Rat

Doxey

Everitt

1977

I The spinal sympathetic outflow to the eyelid, heart, splanchnic blood vessels, vas deferens and anococcygeus muscle was stimulated in pithed rats. 2 Clonidine inhibited sympathetic outflow to all of the tissues studied. The inhibitory effects of clonidine on cardiac nerves and hypogastric nerves were antagonized by phentolamine. 3 Clonidine produced a postsynaptic a-adrenoceptor agonist action on the eyelid, splanchnic blood vessels and the anococcygeus muscle. These effects were also antagonized by phentolamine. 4 The effects of clonidine, naphazoline and oxymetazoline on pre-and postsynaptic a-adrenoceptors were determined. 5 The presynaptic a-adrenoceptors employed were situated in either the sympathetic cardiac or hypogastric nerve terminals. Increases in diastolic blood pressure were used to assess concurrent postsynaptic a-adrenoceptor agonist activity. 6 The presynaptic a-adrenoceptor agonist potencies of clonidine, naphazoline and oxymetazoline were very similar on cardiac nerve terminals whereas on the hypogastric nerve terminals oxymetazoline was about 6 times more potent than either naphazoline or clonidine. 7 The results support the view that presynaptic a-adrenoceptors regulate transmitter release in sympathetic nerves. There appear to be subtle differences between the presynaptic a-adrenoceptors of different sympathetic nerve endings.

“…Although noradrenaline (NA) is present in high concentrations in sympathetic nerve terminals, NA does not mediate all the postjunctional responses elicited by sympathetic nerve stimulation (Ambache & Zar, 1971;Burnstock, 1986). Studies on guinea-pig submucosal arterioles have shown that both the underlying changes in membrane potential (excitatory junction potentials, ej.ps) and vasoconstrictions following short trains of low or high frequency stimulation of the sympathetic nerves are unaffected by ax-adrenoceptor antagonists (Hirst & Neild, 1980;1981;Shen et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Vasoconstriction of guinea‐pig submucosal arterioles following sympathetic nerve stimulation is mediated by the release of ATP

Evans

Surprenant

1992

151

The nature of the transmitter mediating vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve stimulation was studied.2 Prazosin (0.1 pM) abolished the response to exogenously applied phenylephrine (I pM) but had no effect on constrictions of submucosal arterioles evoked by nerve stimulation (100 pulses at 10 Hz). 3 Vasoconstrictions and excitatory junction potentials elicited by nerve stimulation were potentiated by idazoxan (0.1 pM).4 Following reserpine treatment, catecholamine fluorescence was absent in submucosal arterioles but nerve-evoked vasoconstrictions were unaltered. 5 Vasoconstrictions and excitatory junction potentials recorded in response to sympathetic nerve stimulation, as well as constrictions evoked by exogenously applied ATP (3 tiM), were abolished by the P,-purinoceptor antagonist, suramin (100 liM). Suramin had no effect on the vasoconstriction in response to noradrenaline (3 jM), or the nicotinic excitatory postsynaptic potentials (e.p.s.ps) and noradrenergic inhibitory postsynaptic potentials (i.p.s.ps) recorded from submucosal neurones. 6 We conclude that postjunctional responses of submucosal arterioles following sympathetic nerve stimulation are mediated solely through the activation of P2x-purinoceptors by ATP or a related purine nucelotide. The function of neurally released noradrenaline is to act through prejunctional M2-adrenoceptors to depress transmitter release.