On the mechanism of histamine induced enhancement of the cardiac Ca2+ current.
In guinea pig ventricular myocytes, the effect of histamine on the slow Ca2+ current (ICa) was studied and the following results were obtained: (1) Superfusion of cells with histamine resulted in a dose-dependent enhancement of the amplitude of ICa. The threshold concentration of histamine was 10(-8) M, half maximal increase occurred at 3 X 10(-7) M and maximal enhancement (about 3-4-fold) at 5 X 10(-6) M. (2) The histamine effect was greatly reduced by the H2 antagonist cimetidine (10(-5) M) but only slightly by the H1 antagonist diphenhydramine (10(-5) M). (3) Effects of isoprenaline (ISP) and histamine at maximal effective concentrations on ICa were not additive, suggesting that both agents use the same intracellular pathway. Intracellular infusion of a blocker of the cAMP-dependent protein kinase, Rp-cAMPS (10(-4) M), prevented the histamine effect. (4) The involvement of GTP-dependent transducer proteins was studied by cell dialysis with several GTP derivatives. Intracellular application of the stable GDP-analogue, GDP-beta-S, reduced the histamine effect on ICa, whereas the stable GTP analogue, GTP-gamma-S, mimicked the histamine effect.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D006160:Guanosine Triphosphate / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male
D006633:Histamine Antagonists; D007473:Ion Channels; D006632:Histamine; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D002118:Calcium