The role of vagus activity in the presynaptic control of noradrenaline release from rabbit atria.
On various heart preparations with the autonomic innervation left intact, vagus nerve stimulation (VNS) has been found to reduce the amount of noradrenaline (NA) that is released in response to sympathetic nerve stimulation (SNS). The following experiments were carried out on an innervated rabbit perfused atria preparation in which the overflow of NA and acetylcholine (ACh) could be determined simultaneously. VNS impulses applied at a fixed time interval before the corresponding SNS impulses reduced NA overflow when the interval was 3-10 ms (early peak) or 200-283 ms (late peak of inhibition). VNS applied 30-167 ms before SNS had no significant effect ("ineffectual period"). Both inhibitory peaks were abolished by the non-selective muscarine receptor antagonist, atropine. However, atropine did not affect NA overflow during the "ineffectual period" at a 100 ms delay. The hypothesis that the late peak is due to a prostaglandin released secondarily to ACh could not be confirmed because indomethacin had no concentration-dependent differential effect on the late, compared with the early, peak. On the other hand, pirenzepine, a selective M(1) receptor antagonist, converted the "ineffectual period" at 100 ms delay into an inhibition of NA release but failed to alter the early and late inhibitions, respectively. The experiments have revealed a remarkably short latency of the presynaptic muscarinic responses, compared with the postsynaptic ones reported for heart and smooth muscle. It is concluded that both inhibitory peak responses are caused by a single volley of ACh which activates a presynaptic M(2) receptor. Almost simultaneously, a presynaptic M(1) receptor is activated resulting in a facilitation of NA release that partly counteracts the M(2) receptor mediated inhibition. The method which is based on transmitter overflow studies appears to be suitable to resolve presynaptic interactions between two kinds of neurones within a millisecond range.
Muscholl
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Department of Pharmacology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, F.R.G.