Stimulation of phosphatidylinositol metabolism in the isolated, perfused rat heart.
Receptor-stimulated phosphatidylinositol turnover has been studied in isolated, perfused, [3H]inositol-labelled rat hearts by measuring accumulation of inositol phosphates in the presence of lithium chloride. Inositol phosphate accumulation was stimulated by norepinephrine (3 X 10(-5) M) and carbachol (10(-3) M), the increases averaging from 931 +/- 59 (n = 6, mean +/- SEM, cpm/g heart) to 4,165 +/- 609 (n = 6, p less than 0.01) for norepinephrine and to 1,853 +/- 354 (n = 6, p less than 0.05) for carbachol. The norepinephrine stimulation was antagonized by prazosin (10(-7) M) but not by propranolol (10(-7) M), indicating mediation via alpha 1-adrenoceptors. The carbachol stimulation was antagonized by atropine (10(-7) M). The stimulation by norepinephrine was significantly higher in right atria (837 +/- 151 to 6,614 +/- 1,210, n = 6, cpm/g tissue) than in other regions of the heart. Both norepinephrine and carbachol stimulated the formation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate with norepinephrine stimulation being detected as early as 15 seconds. Furthermore, the inositol trisphosphate was identified as the -1,4,5 isomer by anion exchange high-performance liquid chromatography. These data are consistent with the hydrolysis of phosphatidylinositol-(4,5)-bisphosphate yielding inositol-(1,4,5)-trisphosphate. Inositol-(1,3,4)-trisphosphate was not detected in heart preparations, suggesting unusual metabolism of inositol-(1,4,5)-trisphosphate in heart tissue.
Woodcock
E A
EA
Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
White
L B
LB
Smith
A I
AI
McLeod
J K
JK
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010716:Phosphatidylinositols / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology
D002712:Chlorides; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D007294:Inositol; D003994:Bucladesine; D001285:Atropine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D008094:Lithium; D011433:Propranolol; D018021:Lithium Chloride; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin