Influence of cyclooxygenase inhibitors and of lithium on the positive inotropic effect mediated by alpha 1-adrenoceptors in guinea-pig left atrium.
In experiments on the isolated guinea-pig left atrium we tried to get more information about the intracellular signal transmission of the alpha 1-adrenoceptor. We were able to demonstrate that the cyclooxygenase inhibitors indometacin and acetylsalicylic acid enhance the positive inotropic effect of relatively low phenylephrine concentrations at an extracellular calcium concentration of 1.22 mmol/l. Preincubation with prazosin as well as an increased calcium concentration of 2.5 mmol/l abolished this effect. These observations led us to suppose that an elevated level of receptor-generated arachidonic acid, whose degradation is inhibited by the cyclooxygenase inhibitors, caused the increased contractility by releasing more calcium from the sarcoplasmic reticulum. Under these conditions also lithium caused a distinct enhancement of the positive inotropic effect evoked by alpha 1-adrenergic agonists, probably by inhibiting the degradation of the second messenger inositol trisphosphate.
Molderings
G J
GJ
Pharmakologisches Institut, Universitätsklinikum Essen, Federal Republic of Germany.
Schümann
H J
HJ
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D016861:Cyclooxygenase Inhibitors; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D013015:Sotalol / Q000494:pharmacology; D013268:Stimulation, Chemical
D016861:Cyclooxygenase Inhibitors; D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D012110:Reserpine; D008094:Lithium; D013015:Sotalol; D001241:Aspirin; D002118:Calcium; D007213:Indomethacin; D004837:Epinephrine