title: The effect of hypoxia on the phosphorylation of contractile and other proteins in perfused rat heart challenged by isoprenaline.
abstract: Rat hearts perfused with 32Pi were made hypoxic by perfusion with medium gassed with N2/CO2 (19:1). There was a rapid decrease in tension development (25% of control within 40 s), but little change in the frequency of contraction, time to peak tension, or rate of relaxation. The phosphorylation of troponin-I, C-protein and myosin P-light chain was unaffected by 5 min of hypoxia, whereas the proportions of glycogen phosphorylase and pyruvate dehydrogenase in the active form increased slowly. When aerobically perfused hearts were challenged with a bolus (70 pmole) of D,L-isoprenaline, there was a large increase in contractile force, cyclic AMP concentration, phosphorylation of troponin-I and C-protein and activation of phosphorylase and pyruvate dehydrogenase. Hypoxia for 5 min caused a slight, progressive decrease in the response to isoprenaline of force, cyclic AMP and activation of phosphorylase and pyruvate dehydrogenase. In contrast, there was a larger decrease in the phosphorylation of troponin-I and C-protein, suggesting that the activity of cyclic AMP-dependent protein kinase towards the contractile proteins may be impaired by hypoxia. The phosphorylation of myosin P-light chain was unaltered by any condition. The response to hypoxia is compared to that of ischaemia, where a complete loss of the response to isoprenaline occurs after 5 min.
authors.affiliation: Department of Cellular Pharmacology, Smith, Kline & French Research LTD., Herts, U.K.
authors.forename: P J
authors.initials: PJ
authors.lastname: England
authors.forename: E G
authors.initials: EG
authors.lastname: Krause
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002395:Catecholamines / Q000494:pharmacology; D003285:Contractile Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D006005:Phosphorylases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002395:Catecholamines; D003285:Contractile Proteins; D011768:Pyruvate Dehydrogenase Complex; D000242:Cyclic AMP; D006005:Phosphorylases; D011494:Protein Kinases; D007545:Isoproterenol; D002118:Calcium