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Evidence against presynaptic α-adrenoreceptor modulation of cardiac sympathetic transmission

Nature volume 286, pages 288–291 (1980)Cite this article

Abstract

In addition to its well known actions on postsynaptic adrenoreceptors, noradrenaline released at the sympathetic nerve endings is now believed to modulate subsequent transmitter release through its actions on presynaptic receptors1–7. Much evidence in support of this hypothesis has been obtained from overflow studies in which labelled noradrenaline and metabolites released into the bathing solution are used as an assay of transmitter release. According to Langer4 and Rand, McCulloch and Story6, evidence to favour the existence of such a presynaptic mechanism includes the demonstration that α-adrenoreceptor antagonists produce enhanced transmitter overflow in steady-state conditions of sympathetic stimulation. They also suggest that α-adrenoreceptor-mediated potentiation of transmitter release would not be expected in response to a single pulse, as a threshold concentration of released noradrenaline is required to activate presynaptic inhibition of further release. In the myocardium both conditions have been obtained in the presence of phenoxybenzamine5,6. Surprisingly, although phentolamine is also a potent α-adrenoreceptor antagonist, the potentiation of transmitter release was less than the increase due to phenoxybenzamine6. Studies of transmitter overflow have generally been made with supraphysiological sympathetic stimulation of 5 Hz continuously for 30s or 4 Hz for 60s (refs 6,7). We have used more closely physiological stimulation parameters delivered only during the atrial refractory period. We have now shown that phenoxybenzamine markedly potentiates the chronotropic response to a single pulse and also responses up to maximum stimuli. By contrast, phentolamine and yohimbine were totally without effect even at high concentration. The action of phenoxybenzamine was largely accounted for by its effect on uptake blockade. Taken together, our studies provide evidence against a physiological role of presynaptic α-adrenoreceptors in the heart

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  1. Baker Medical Research Institute, Commercial Road, Prahran, Victoria, Australia, 3181

    James A. Angus & Paul I. Korner

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  1. James A. Angus
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Angus, J., Korner, P. Evidence against presynaptic α-adrenoreceptor modulation of cardiac sympathetic transmission. Nature 286, 288–291 (1980). https://doi.org/10.1038/286288a0

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