Identification of the neuroeffector transmitter in jejunal branches of the rabbit mesenteric artery

Abstract

Vasoconstriction or excitatory junction potentials (e.j.ps) evoked by nerve stimulation (15 field pulses at 2 Hz every 3 min) were recorded in rabbit isolated jejunal arteries. The resting diameter of the arteries and its decrease in response to stimulation was measured by a photoelectric method. Vasoconstriction was insensitive to prazosin 0.1 or 1 mumol/l. Yohimbine 1 mumol/l considerably enhanced, whereas alpha,beta-methylene ATP (alpha,beta-meATP) 1 mumol/l abolished the contractile response. In order to test the effect of exogenously applied transmitter candidates, noradrenaline (0.1-1 mumol/l) and ATP (10-30 mumol/l) were added in concentrations which evoked a vasoconstriction comparable to that induced by electrical stimulation. The action of noradrenaline was prevented by prazosin 0.1 mumol/l, but was unaffected by both yohimbine 1 mumol/l and alpha,beta-meATP 1 mumol/l. Alpha,beta-meATP 1 mumol/l depressed the effect of ATP. The e.j.ps evoked by a train of 15 pulses showed facilitation up to the third response and thereafter depression; a partial summation was also observed. Prazosin 0.1 mumol/l did not change the e.j.p. amplitudes. By contrast, when yohimbine 0.1 or 1 mumol/l was added to the prazosin-containing medium, both the late e.j.ps in the train and the summation were enhanced in a concentration-dependent manner. Alpha,beta-meATP 1 mumol/l almost abolished the e.j.ps. In conclusion, in rabbit jejunal arteries, stimulation of postganglionic sympathetic nerves may release noradrenaline together with ATP which is probably the sole neuroeffector transmitter under our conditions. Transmitter release seems to be modulated by the activation of presynaptic alpha 2-adrenoceptors. Under the stimulation conditions of the present experiments the released transmitter does not activate postsynaptic alpha 1-adrenoceptors.

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

“…In contractility experiments, magnesium was omitted from the solution because constrictions in response to nerve stimulation or exogenously applied agonists were greater; similar observations have been reported in a variety of other blood vessels (Ramme et al, 1987;Evans & Cunnane, 1991). Test agents were added to '."…”

“…However it is usually only a component that is resistant. Purely aresistant contractions in response to short trains of low frequency stimuli have been reported in two vessels, the rabbit jejunal artery (Ramme et al, 1987;Evans & Cunnane, 1992) and the rabbit saphenous artery ; even in these vessels a substantial component of the contraction can be demonstrated to be noradrenergic in origin following prolonged high frequency stimulation. The present study on the guinea-pig submucosal arterioles has failed to reveal an a-adrenoceptor-sensitive component of the vasoconstriction at stimulation parameters that have demonstrated a substantial noradrenergic contraction in all arteries studied to date.…”

“…In a number of other arteries cx-adrenoceptor antagonist resistant contractions following sympathetic nerve stimulation have been recorded (Muramatsu et al, 1989;Sjoblom-Widfeldt et al, 1990;Brizzolara & Burnstock, 1990). These are thought to be due to ATP, which is co-released with NA, acting through P2x-purinoceptors because they are abolished following desensitization of P2x-purinoceptors with the stable adenosine 5'-triphosphate (ATP) analogue cxj-methylene ATP (Ramme et al, 1987;Hirst & Jobling, 1989;Evans & Cunnane, 1992). Recently the trypanocide, suramin, has been demonstrated to be an antagonist at the P2-purinoceptor in the rodent vas deferens (Dunn & Blakeley, 1988; Kugelgen & Starke, 1989) and the guinea-pig taenia caeci (Den Hertog et al, 1989;Hoyle et al, 1990).…”

Purinergic receptors in the splanchnic circulation

“…In what concerns the splanchnic circulation, the first description of such corelease was reported by Su [164] in the rabbit portal vein. Since then, growing evidence emerged that ATP is a cotransmitter in the splanchnic circulation of the dog [9,94,113,114,144,170], rabbit [140,181], guinea-pig [8], and rat [19,37,44].…”

Involvement of ETA receptors in the facilitation by endothelin‐1 of non‐adrenergic non‐cholinergic transmission in the rat urinary bladder

“…The most solid evidence supporting ATP as a neurotransmitter is derived from investigations in the vas deferens (Fedan et al, 1981;Meldrum & Burnstock, 1983;Sneddon & Burnstock, 1984;Sneddon & Westfall, 1984;Stjmrne & Astrand, 1984), the mesenteric artery (Ramme et al, 1987), and the rat bladder (Burnstock et al, 1978b;Kasakov & Burnstock, 1983;Hoyle & Burnstock, 1985;Acevedo & Contreras 1985).…”