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Different muscarinic receptors mediate autoinhibition of acetylcholine release and vagally-induced vasoconstriction in the rat isolated perfused heart

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Summary

Experiments were carried out on rat isolated perfused hearts with both vagus nerves attached. The acetylcholine stores were labelled with [14C]-choline. The effects of muscarinic receptor antagonists on the [14C]overflow and increase in perfusion pressure evoked by vagus nerve stimulation (10 Hz, 4–10 mA) were studied in order to determine the muscarinic receptor type involved in autoinhibition of acetylcholine release and vagally-induced vasoconstriction in the rat heart.

Stimulation of the vagus nerves (1200 pulses) caused an increase in [14C]-overflow and in perfusion pressure which was significantly reduced by hexamethonium 500 μmol/l and abolished by tetrodotoxin 0.3 μmol/l or perfusion with Ca2+-free solution. The fractional rate of evoked [14C]-overflow per pulse upon stimulation at 10 Hz (720 pulses) was doubled in the presence of the non-selective antagonist atropine (0.01–1 μmol/l) as well as in that of the M2-selective compounds methoctramine (0.1 μmol/l) and AF-DX 116 (0.1–1 μmol/l), but remained unaffected by the M3-selective hexahydrosiladifenidol (0.1 μmol/l). The increase in perfusion pressure upon nerve stimulation was reduced by atropine (0.01 μmol/l) or hexahydrosiladifenidol (0.1 μmol/l) to approximately 50% and increased by about 50% in the presence of AF-DX 116 (0.1 μmol/l).

The results show that the autoinhibition of acetylcholine release in the rat heart is mediated by M2 receptors. On the other hand, the increase in perfusion pressure upon vagus nerve stimulation is caused by a different muscarinic receptor, more sensitive to hexahydrosiladifenidol than to M2-selective antagonists.

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, D-6500, Mainz, Germany

    I.T. Bognar, B. Beinhauer, P. Kann & H. Fuder

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  1. I.T. Bognar
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  2. B. Beinhauer
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  3. P. Kann
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  4. H. Fuder
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Bognar, I., Beinhauer, B., Kann, P. et al. Different muscarinic receptors mediate autoinhibition of acetylcholine release and vagally-induced vasoconstriction in the rat isolated perfused heart. Naunyn-Schmiedeberg's Arch Pharmacol 341, 279–287 (1990). https://doi.org/10.1007/BF00180652

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  • DOI: https://doi.org/10.1007/BF00180652

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