THE NOREPINEPHRINE-STIMULATED INOSITOL PHOSPHATE RESPONSE IN HUMAN ATRIA

Inositol phosphate release and metabolism were studied in right atrial appendages obtained from 18 patients undergoing coronary artery bypas s surgery and/or mitral valve replacement. [H-3]Inositol-labeled human atria contained inositol(1,4, 5)trisphosphate, inositol(1,4)bisphosph ate and the 1- (or 3) and 4-isomers of inositol monophosphate. Additio n of norepinephrine (100 mu mol/l) activated the release of inositol p hosphates, as indicated by increased [H-3]inositol label in all of the se inositol phosphates. However, the phosphorylation product of inosit ol (1,4,5)trisphosphate, inositol-(1,3,4,5)tetrakisphosphate, and its metabolic products were not detected, either in control or stimulated atria, Similar inositol phosphate profiles were observed in rat right atria. Furthermore, both human and rat atria contained high concentrat ions of inositol(1,4,5)trisphosphate, which were not observed to incre ase with norepinephrine stimulation. The inositol phosphate responses to norepinephrine in rat and human cardiac tissue appear to be similar , except for the generally lower activity observed in human tissue. Th us, the rat provides a suitable model for the study of cardiac phospha tidylinositol turnover. (C) 1995 Academic Press Limited