Summary
The influence of pertussis toxin on the effects of adenosine, the adenosine receptor agonist (−)-N6-phenylisopropyladenosine (PIA) and the m-cholinoceptor agonist carbachol on heart rate and atrioventricular (AV) conduction was investigated in spontaneously beating isolated perfused guinea-pig hearts. In addition, the effects of the agents on the electrocardiogram recorded from anesthetized guinea pigs were studied. Adenosine (0.1–100 μmol/l) and PIA (0.001–100 μmol/l) had concentration-dependent negative chronotropic and negative dromotropic effects. These effects were prevented by pretreatment of the animals with pertussis toxin (150 μg/kg; i.v.). Carbachol (0.001–100 μmol/l) had similar cardiac depressant effects. These effects were also abolished by pertussis toxin. In contrast, the negative chronotropic and negative dromotropic effects of the calcium antagonist verapamil which was investigated for comparison were not influenced by pretreatment with pertussis toxin. Since the cardiac depressant effects mediated via adenosine receptors or via m-cholinoceptors are most probably due to an activation of a K+ conductance, it is concluded that both receptors in the sinus node and in the AV node may be coupled via a common pertussis toxin-sensitive guanine nucleotide-binding protein to the K+ channel. It remains to be elucidated whether an additional inhibitory coupling to Ca2+ channels also plays a role.
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Parts of the results have been presented in oral form at the 3rd International Symposium on Adenosine at Munich (Schmitz et al. 1986a) and at the Joint Meeting of the German Pharmacological Society and the Swiss Society for Pharmacology and Toxicology at Mannheim (Schmitz et al. 1986b)
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Böhm, M., Schmitz, W., Scholz, H. et al. Pertussis toxin prevents adenosine receptor- and m-cholinoceptor-mediated sinus rate slowing and AV conduction block in the guinea-pig heart. Naunyn-Schmiedeberg's Arch Pharmacol 339, 152–158 (1989). https://doi.org/10.1007/BF00165137
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DOI: https://doi.org/10.1007/BF00165137