Possible feed-back inhibition of noradrenaline release by purine compounds

Abstract

The contractile responses to transmural stimulation of, and the overflow of tritium from the rat portal vein prelabelled with 3H-noradrenaline were studied. The contractile responses of the rat portal vein were sustained throughout the period of stimulation. The tension developed did not decline when two consecutive periods of stimulation were compared. In contrast, the tritium overflow decreased during the second period of stimulation. Preincubation with 3 micronM phenoxybenzamine during 30 min increased 3-fold the tritium overflow during stimulation. Phentolamine and phenoxybenzamine were nearly equipotent in reducing the vascular response to stimulation. In contrast, phentolamine was less potent than phenoxybenzamine in increasing the 3H-noradrenaline overflow elicited by stimulation. The results obtained with phentolamine are interpreted in terms of a different potency of phentolamine to produce blockade of prejunctional and postjunctional alpha-adrenoceptors in the rat portal vein. ATP inhibited by 70% the tritium overflow induced by stimulation. The potency of ATP in inhibiting the overflow increased when the prejunction alpha-adrenoceptors were blocked. The purine compounds ATP, ADP, AMP and adenosine were roughly equipotent in inhibiting stimulation-induced tritium overflow. The tritium released by stimulation decreased when uptake and metabolism of adenosine were inhibited. Under physiological conditions, a prejunctional purinergic inhibition of noradrenaline release might be involved in an endogenously mediated negative feed-back regulatory mechanism. It is possible that the purinergic inhibition of the noradrenaline liberation elicited by stimulation plays a physiological role in tissues with both purinergic and adrenergic innervation.

4‐aminopyridine Blockade of Neuronal Depressant Responses to Adenosine Triphosphate

“…Adenosine in particular is a potent inhibitor of transmitter release (Ginsborg & Hirst, 1972;Hedqvist & Fredholm, 1976;Vizi & Knoll, 1976;Clanachan, Johns & Paton, 1977;Enero & Saidman, 1977;Hollins & Stone, 1979) and such an effect could explain this action of 4-AP whether or not the interaction occurs at the level of the potassium channel.…”

Indirect evidence that purinergic modulation of perivascular adrenergic neurotransmission in the portal vein is a physiological process

“…Furthermore, adrenergic neurotransmission has been shown to be modulated by a number of other pharmacological agents including adenine nucleosides and nucleotides. Adenosine 5'-triphosphate (ATP) and adenosine selectively de-press the response to sympathetic nerve stimulation in several isolated blood vessels including rabbit portal vein (Su, 1978;Brown etal., 1982) and rat portal vein (Enero & Saidman, 1977;Wakade & Wakade, 1978;Moylan & Westfall, 1979;Enero, 1981). These compounds also inhibit sympathetic neurotransmission in various visceral preparations (see Burnstock & Brown, 1981 The portal vein receives a dense adrenergic innervation in the rabbit, rat and guinea-pig (Bumstock et al, 1979;Johansson et al, 1970).…”

Adenosine Inhibition of Γ‐aminobutyric Acid Release From Slices of Rat Cerebral Cortex

“…This action has been studied at both cholinergic (Ginsborg & Hirst, 1972; Ribeiro & Walker, 1975;Sawynok & Jhamandas, 1976;Vizi & Knoll, 1976;Gustafsson, Hedqvist, Fredholm & Lundgren. 1978) and adrenergic (Hedqvist & Fredholm, 1976;Clanachan, Johns & Paton, 1977;Enero & Saidman, 1977;Verhaeghe, Vanhoutte & Shepherd, 1977;Su, 1978;Paton, Bar, Clanachan & Lauzon, 1978) terminals in the peripheral nervous system. It has recently been concluded that adenosine can also reduce acetylcholine release at the synapse between motor axon collaterals and Renshaw cells (Lekic, 1977), and noradrenaline release from terminals in the cerebral cortex in vivo (Taylor & Stone, 1980) and in vitro (Harms, Wardeh & Mulder, 1978 (Bowery & Brown, 1974 …”