Effects of platelet activating factor on contractile force and 45Ca fluxes in guinea-pig isolated atria.
1. The effects of platelet activating factor (PAF) were studied on the electromechanical properties and 45Ca2+ fluxes of guinea-pig isolated atria. 2 Both in spontaneously beating and electrically driven atria, PAF (10(-12)-10(-7) M) increased atrial rate but produced a biphasic effect on contractile force. At low concentrations (up to 10(-10) M) it produced a positive inotropic effect, while at higher concentrations PAF exerted a negative inotropic effect. A similar biphasic effect was observed in the slow contractions elicited by isoprenaline in K(+)-depolarized atrial fibres. 3. The positive inotropic effect of PAF was prevented by verapamil, whereas pretreatment of atria with propranolol, phentolamine, indomethacin or atropine did not modify its positive and negative inotropic actions. BN 52021, a specific PAF antagonist, abolished both the positive and negative inotropic effects. 4. PAF had no effect on the characteristics of the action potentials recorded in either normally polarized or K(+)-depolarized (slow action potential) atrial fibres. 5. At concentrations at which it increased contractile force, PAF potentiated the contractile responses to Ca2+ (0.9-9 mM), whereas at negative inotropic concentrations it inhibited them. The negative inotropic effect of PAF was partially reversed in 70% Na+ medium. 6. At 10(-11) M, PAF increased 45Ca2+ uptake and reduced the rate coefficient (kcm) for the 45Ca2+ efflux. This increase in 45Ca2+ uptake was abolished in atria pretreated with verapamil or BN 52021. However, 10(-7) M PAF modified neither 45Ca2+ uptake nor efflux in atrial muscle. 7. These results suggest that in guinea-pig atria the biphasic inotropic effects of PAF cannot be explained through modifications in the slow inward Ca2+ current or in Na'-Ca2+ exchange, but may be related to changes in trans-sarcolemmal Ca2 + entry mediated by specific PAF receptors.
Diez
J
J
Instituto de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Delpón
E
E
Tamargo
J
J
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes; D005260:Female; D046934:Ginkgolides; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002132:Calcium Radioisotopes; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D012964:Sodium; D014700:Verapamil; C045856:ginkgolide B; D002118:Calcium