Alpha 1-adrenoceptor stimulation reduced the positive chronotropic effect of simultaneously administered beta-adrenoceptor- and H2-receptor agonists in guinea-pig right atria.
The modulatory influence of alpha 1-adrenoceptor agonists on the beta-adrenoceptor-mediated or H2-receptor-mediated positive chronotropic effect was investigated in isolated guinea-pig right atria. In the presence of cirazoline, the isoprenaline- or impromidine-induced positive chronotropic effect was significantly reduced. Methoxamine also reduced the isoprenaline-induced positive chronotropic effect. The reduction was abolished by the alpha 1-adrenoceptor antagonist prazosin. The protein kinase C activator phorbol-12-myristate-13-acetate, as well as the protein kinase inhibitor polymyxin B, had no influence on the cirazoline-evoked decrease of the beta-adrenoceptor-mediated positive chronotropic effect. Cirazoline, in the absence of isoprenaline or impromidine, concentration-dependently decreased heart rate, which could not be abolished by phentolamine and prazosin. Stimulation of alpha 1-adrenoceptors by phenylephrine in the presence of the beta-adrenoceptor antagonist sotalol, decreased spontaneous heart rate. The decrease was abolished by prazosin as well as by pretreatment with the neurotoxin 6-hydroxy-dopamine. The decrease in heart rate may to some extent be the result of interactions at the level of signal transduction systems of the 3 receptors.
Molderings
G J
GJ
Pharmakologisches Institut, Universitätsklinikum Essen, F.R. Germany.
Schümann
H J
HJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000502:physiology*; D013015:Sotalol / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D007093:Imidazoles; D011970:Receptors, Histamine H2; D010656:Phenylephrine; D015016:Yohimbine; D013015:Sotalol; D008729:Methoxamine; D011112:Polymyxin B; D007545:Isoproterenol; C014282:cirazoline