title: The effects of histamine on contraction frequency, sodium influx, and cyclic AMP in cultured rat heart cells.
abstract: Histamine has been shown to have both positive inotropic and chronotropic effects. To evaluate the chronotropic effects, spontaneously contracting monolayers of cultured rat myocardial cells were treated with histamine, 10(-7) M-10(-4) M. This resulted in a dose-dependent increase in contraction frequency reaching a maximum in 10(-5) M histamine. Contraction frequency (mean +/- SEM) increased from a control of 121 +/- 5 contractions per minute to 153 +/- 4.5, 181 +/- 9, 212 +/- 4, and 216 +/- 1 in 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M histamine, respectively (for each n = 10, p less than 0.001). The effect was time-dependent, taking 30 minutes to develop fully. Changes in contraction frequency were accompanied by parallel dose- and time-dependent increases in the verapamil-sensitive sodium influx. Verapamil-sensitive sodium influx (pmol/cm2/sec) increased from a control of 10.45 +/- 1.44 (mean +/- SEM) to 24.34 +/- 2.41 and 32.57 +/- 2.35 at 10- and 30-minute treatment with 10(-6) M histamine (n = 5, p less than 0.001). These data fit the previously described relation between verapamil-sensitive sodium influx and contraction frequency in these cells. Cimetidine (10(-4) M) but not diphenhydramine (10(-4) M) abolished both the contraction frequency and sodium influx response to histamine. Subsequent studies showed a dose- and time-dependent elevation of cyclic adenosine monophosphate (cAMP) with histamine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004155:Diphenhydramine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology*; D007097:Imines / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D007097:Imines; D002927:Cimetidine; D006632:Histamine; C014925:RMI 12330A; D004155:Diphenhydramine; D012964:Sodium; D014700:Verapamil; D000242:Cyclic AMP