Influence of prostacyclin and two metabolites on the contractility of cultured rat heart cells.
Heart cells were cultured from newborn rats, and the contractile activity (CA) and beating frequency (BF) were recorded using an electrooptical technique. Myocardial cells were found to be highly sensitive to Prostacyclin (PGI2) since a 10(-11) M concentration increased the BF and CA. Increasing the concentration (2.7 x 10(-10) to 2.7 x 10(-8) M) resulted in a dose-dependent decrease in CA and BF. The stable product of the non-enzymatic degradation of PGI2 (6 Keto PGF1 alpha) was found to be completely ineffective, and the stable product of the enzymatic PGI2 metabolism (6 Keto PGE1) exerted only a dose-dependent (10(-6) to 10(-5) M) positive inotropic effect. PGI2 was also effective in the presence of serum instead of culture medium but the decrease in CA was less marked than in culture medium, probably due to protein-binding of the drug. When the CA was decreased by PGI2, perfusion with the intracellular calcium-releasing and phosphodiesterase inhibiting agent, caffeine, reversed the PGI2-induced negative inotropic effect. These results suggest that PGI2 participates in the regulation of the heart cell contractility. Its metabolite 6 Keto PGEI could also influence heart cell contractility but higher concentrations are needed. Moreover myocardial intracellular calcium availability seems to be influenced by PGI2.
Auclair
M C
MC
Institut de Pharmacologie, U228 INSERM, 15, Paris, France.
Vernimmen
C
C
Lechat
P
P
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology*; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002478:Cells, Cultured; D011464:Epoprostenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D002110:Caffeine; D015121:6-Ketoprostaglandin F1 alpha; C022950:6-ketoprostaglandin E1; D011464:Epoprostenol; D000527:Alprostadil