Role of Na+/phosphate-cotransporter in myocardial contractile responses to alpha 1-agonist.
The interaction of cardiac sodium/phosphate (Na+/Pi)-cotransporter and the phosphoinositide pathway (PIP) in influencing myocardial contraction was investigated. Specifically, the study was performed to determine if myocardial positive inotropic response (+dP/dt) to phenylephrine (PE, an activator of PIP) can be potentiated by inorganic phosphate (Pi, the substrate of Na+/Pi-cotransporter). Contractile responses of the isolated perfused rat heart were studied in conditions of controlled extracellular calcium activity and constant preload. The data showed that phenylephrine-induced increase in +dP/dt was potentiated by Pi. Prazosin inhibited this increase in +dP/dt, indicating alpha 1-adrenergic involvement. This Pi-potentiated increase in +dP/dt was also inhibited by phosphonoformate (PFA); however, only partial inhibition was obtained with concentrations of PFA that selectively inhibited Na+/Pi-cotransporter. Isoproterenol-induced increase in +dP/dt was not potentiated by Pi, showing that potentiation of +dP/dt is not a common effect of Pi. The data support an important interaction between PIP and Na+/Pi-cotransporter in regulating myocardial contraction.
Onwochei
M O
MO
Department of Pharmacology and Therapeutics, Medical College of Ohio, Toledo 43699-0008, USA.
D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D004558:Electric Stimulation; D017245:Foscarnet / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D002352:Carrier Proteins; D007295:Inositol Phosphates; D010710:Phosphates; D011942:Receptors, Adrenergic, alpha; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D010656:Phenylephrine; D017245:Foscarnet; D007545:Isoproterenol; D002118:Calcium; D011224:Prazosin