6533b839fe1ef96bd12a6e60

RESEARCH PRODUCT

Cholinergic–Adrenergic Presynaptic Interactions in the Heart and Characterization of the Receptors Involved

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ABSTRACT The rabbit perfused atria preparation with the extrinsic sympathetic and vagus innervation intact has been used to study the mutual interactions between the two branches of the autonomic nervous system by measuring the respective transmitter overflow rates upon electrical stimulation. Using this method the stimuli exciting vagus and sympathetic nerves can be applied at selected time intervals which provides an advantage over the common method of field stimulation where all kinds of neurons are stimulated simultaneously. In the absence of drugs, presynaptic interactions resulting in a decreased noradrenaline overflow occurred when the vagal stimuli preceded the sympathetic ones by 3-10 ms which is an extremely short latency for a muscarinic response. A second period of muscarinic inhibition of noradrenaline overflow was observed at a pulse-to-pulse distance of 200-283 ms. Vagus impulses applied 100 ms before the sympathetic ones had no effect but caused an inhibition of noradrenaline overflow in the presence of pirenzepine 5.7-80 nM. Pirenzepine 80 nM did not modify the inhibitory responses at 3 and 283 ms. Thus, at the 100 ms pulse-to-pulse interval an M 1 receptor mediated facilitation of noradrenaline overflow is present which counteracts the M 2 receptor mediated inhibition extending from the 3 ms to the 283 ms pulse-to-pulse interval. Correspondingly, selective blockade of the M 2 receptor by AF–DX 116 0.4-0.8 μM revealed a facilitation of noradrenaline overflow when the vagus impulses preceded the sympathetic ones by 100 ms. The M 2 autoreceptor inhibiting acetylcholine release is activated by lower synaptic concentrations of the transmitter than the M 2 heteroreceptor inhibiting noradrenaline release.