Presynaptic α₂‐autoinhibition in a vascular neuroeffector junction where ATP and noradrenaline act as co‐transmitters

Abstract

1 a2-Autoinhibition of transmitter release was investigated in the largest rami caecales of the rabbit ileocolic artery. Vasoconstriction, elicited by electrical field stimulation or by exogenous agonists, was measured as an increase in perfusion pressure. 2 Short periods of electrical stimulation elicited monophasic vasoconstriction, whereas longer periods (> 10s) produced biphasic vasoconstriction. Prazosin had no significant effect on the first component of the biphasic vasoconstriction elicited by electrical stimulation, but did reduce the second component at higher frequencies. a,fi-Methylene ATP significantly attenuated the first component whilst the second component was relatively resistant. 3 The x2-adrenoceptor antagonist yohimbine did not change responses evoked by very short pulse trains (<2 s) but enhanced responses to longer pulse trains. When vasoconstriction was biphasic, both phases were potentiated by yohimbine. 4 The results indicate that the vasoconstriction elicited by brief trains of sympathetic nerve impulses is mainly or exclusively mediated by ATP, whereas at longer pulse trains a noradrenergic component comes into play. The potentiation produced by yohimbine is due to interruption of presynaptic a2-adrenoceptor-mediated autoinhibition of transmitter release. The autoinhibition affects both purinergic and adrenergic components of sympathetic neurotransmission.

Modulation of non‐adrenergic non‐cholinergic inhibitory neurotransmission in rat gastric fundus by the α2‐adrenoceptor agonist, UK‐14,304

“…If, in the rat gastric fundus, NO and VIP are released from the same neurones, which is probable in the guinea-pig small intestine (Costa et al, 1991), the presynaptic influence of the a2-adrenoceptor agonist UK-14,304, on these cotransmitters is the same. Examples of a differential influence of a presynaptic mechanism on cotransmitters have been obtained (Ellis & Burnstock, 1989;Bulloch & Starke, 1990).…”

Effect of 7‐nitro indazole on neurotransmission in the rat vas deferens: mechanisms unrelated to inhibition of nitric oxide synthase

“…The rat isolated vas deferens preparation possesses both prejunctional M2- (Bullock & Starke, 1990;Brown et al, 1979) and postjunctional M2-adrenoceptors (Ganguly & Bhattacharya, 1969;Lotti et al, 1980) activation of either of which would be expected to reduce the size of contractions due to field stimulation. In this study, yohimbine (1 jM) failed to reverse the inhibitory effect of 7-NI on the field stimulated rat vas deferens.…”

Purinergic receptors in the splanchnic circulation

“…Modulation of ATP release by noradrenaline can only be revealed during nerve stimulation of very low frequencies (0.2±2 Hz) and short duration (10 s) [9,117]. Parallel with what has been described on transmitter release, the neurogenic contractions induced by electrical field stimulation of postganglionic sympathetic nerves within splanchnic vessels are biphasic [16,94,144,154]. In dog [115] and rabbit mesenteric arteries [181], the first component is purinergic in nature, develops rapidly, is transient and predominates at low frequencies (1-2 Hz) of stimulation, whereas the second component is adrenergic, develops after the purinergic one, is more long-lasting and becomes more evident as the frequency of stimulation increases (10 Hz).…”

“…Differential autoinhibition has been suggested in the rat mesenteric artery [41]. In the rabbit ileocolic artery, activation of presynaptic α 2 -adrenoceptors preferentially inhibits the release of noradrenaline [16]. In canine splenic arteries, adrenergic neuron blockade with guanethidine [189] or inhibition of sodium channels by tetrodotoxin [188] mainly depresses the adrenergic rather than the purinergic component.…”