Protein kinase inhibitors attenuate cardiac swelling-induced amino acid release in the rat.
Rat Langendorff heart preparations have been used to study the efflux of cardiac amino acids into coronary artery perfusates during brief (5-min) periods of exposure to hyposmotic stress (70 mM NaCl). Coronary flow rates, heart rates and intra-aortic pressures were recorded. Amino acid levels were measured by high-performance liquid chromatography. Hyposmotic stress caused marked percentage increases in taurine, glutamate and aspartate levels in the coronary perfusate, with smaller increases in phosphoethanolamine, glycine and alanine and non-significant increases in serine and glutamine. Amino acid levels declined during reperfusion with isosmotic Krebs-Henseleit bicarbonate buffer. Inhibition of protein kinase C with chelerythrine chloride (5 microM) depressed the osmotically-induced release of aspartate, glutamate, taurine and glycine. The protein tyrosine kinase inhibitor, genistein, reduced the anisosmotic efflux of aspartate, glutamate, taurine and phosphoethanolamine. Lavendustin A, another inhibitor of tyrosine kinase, depressed the osmotically evoked release of aspartate, glutamate and taurine. These studies demonstrate the involvement of protein kinase C and tyrosine kinases in the efflux of amino acids from the osmotically challenged rat heart and imply that these enzymes are involved in the mechanisms responsible for volume regulation by cardiac cells.
Song
D
D
Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201-1928, USA.
O'Regan
M H
MH
Phillis
J W
JW
D000470:Alkaloids; D000596:Amino Acids / Q000378:metabolism*; D000758:Anesthesia; D000818:Animals; D053119:Benzophenanthridines; D002306:Cardiac Volume / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D066298:In Vitro Techniques; D009995:Osmosis / Q000502:physiology; D010477:Perfusion; D010617:Phenanthridines / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D000596:Amino Acids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D010636:Phenols; C062898:lavendustin A; D019833:Genistein; C016299:chelerythrine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C