Phosphorylation of the 19,000-dalton light chain of myosin in perfused rat heart under the influence of negative and positive inotropic agents.

Sj, Kopp; Bárány, Michael

doi:10.1016/s0021-9258(19)86419-0

Cited by 90 publications

(4 citation statements)

References 32 publications

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“…Myocardial contractile performance measured under ex vivo conditions in hearts from rats administered lead (5 ,ug/mL drinking water) for 20 months was shown to be depressed significantly (38,39). This effect of lead was linked to disturbances in myocardial energy metabolism and defective phosphorylation of putative regulatory phosphoproteins suspected of being involved in the regulation of chemicomechanical energy transduction in heart muscle (38,47,48).…”

Section: Contractile and Metabolic Actionsmentioning

confidence: 99%

Cardiovascular actions of lead and relationship to hypertension: a review.

Kopp¹,

Barron²,

Tow³

1988

Environ Health Perspect

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Chronic and acute lead poisoning cause overt, clinical symptoms of cardiac and vascular damage with potentially lethal consequences. Morphological, biochemical, and functional derangements of the heart have all been described in patients following exposure to excessive lead levels. Disturbances in cardiac electrical and mechanical activity and postmortem evidence of morphological and biochemical derangements of the myocardium have all been reported following excessive exposure to lead in humans. In addition, signs of vascular degeneration, abnormal vascular smooth muscle function, and altered vessel compliance have been described in humans chronically and acutely exposed to toxic lead levels. Similar cardiovascular complications have been detected following excessive lead exposure in experimental animals. Myocarditis, electrocardiographic disturbances, heightened catecholamine arrhythmogenicity, altered myocardial contractile responsiveness to inotropic stimulation, degenerative structural and biochemical changes affecting the musculature of the heart and vasculature, hypertension, hypercholesterolemia, atherosclerosis, and increased vascular reactivity to alpha-adrenergic agonists have been among the reported cardiovascular disturbances linked to lead poisoning. Less certain are the cardiovascular effects of subclinical lead poisoning. Although controversial, chronic low-level lead exposure has been linked to hypertension and other cardiovascular disturbances in both clinical and experimental studies. In general, it can be concluded that lead over a wide range of exposure intensities can induce significant changes in the function of the cardiovascular system. Evidence points to the involvement of multiple sites of action. Cardiac and vascular sites, as well as sites within the central nervous system, have all been implicated in the sequelae of cardiovascular effects. The exact pathogenic mechanisms that underlie the actions of lead in the cardiovascular system, however, have yet to be elucidated definitively.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Contractile and Metabolic Actionsmentioning

confidence: 99%

Cardiovascular actions of lead and relationship to hypertension: a review.

Kopp¹,

Barron²,

Tow³

1988

Environ Health Perspect

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“…Isoprenaline (0.1 tM) was then infused and at the peak of the positive inotropic response, the hearts were freeze-clamped with precooled (-196 °C) Wollenberger clamps, powdered, and stored under liquid N2 (Kranias & Solaro, 1982). The specific radioactivity of [32P]ATP in hearts perfused with [32P]Pi was determined from the specific radioactivity of [32p]_ phosphocreatine (Kopp & Barany, 1979) at the end of the perfusion. There was no significant change in the specific activity of [y-32P]ATP among hearts perfused on a particular day with the same stock solution of [32P]Pi (the ratio of the low and high values in a typical group was about 0.8).…”

Section: Heart Perfusionmentioning

confidence: 99%

Phosphorylation of phospholipids in isolated guinea pig hearts stimulated with isoprenaline

Jakab

Rapundalo

Solaro³

et al. 1988

Biochemical Journal

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Phosphorylation of phospholipids was studied in Langendorff perfused guinea pig hearts subjected to beta-adrenergic stimulation. Hearts were perfused with Krebs-Henseleit buffer containing [32P]Pi and freeze-clamped in a control condition or at the peak of the inotropic response to isoprenaline. 32P incorporation into total phospholipids, individual phospholipids and polyphosphoinositides was analysed in whole tissue homogenates and membranes, enriched in sarcoplasmic reticulum, prepared from the same hearts. Isoprenaline stimulation of the hearts did not result in any significant changes in the levels of phosphate incorporation in the total phospholipid present in cardiac homogenates (11.6 +/- 0.4 nmol of 32P/g for control hearts and 12.4 +/- 0.5 nmol of 32P/g for isoprenaline-treated hearts; n = 6), although there was a significant increase in the degree of phospholipid phosphorylation in sarcoplasmic reticulum (3.5 +/- 0.3 nmol of 32P/mg for control hearts and 6.7 +/- 0.2 nmol of 32P/mg for isoprenaline-treated hearts; n = 6). Analysis of 32P incorporation into individual phospholipids and polyphosphoinositides revealed that isoprenaline stimulation of the hearts was associated with a 2-3-fold increase in the degree of phosphorylation of phosphatidylinositol monophosphate and bisphosphate as well as phosphatidic acid in both cardiac homogenates and sarcoplasmic reticulum membranes. In addition, there was increased phosphate incorporation into phosphatidylinositol in sarcoplasmic reticulum membranes. Thus, perfusion of guinea pig hearts with isoprenaline is associated with increased formation of polyphosphoinositides and these phospholipids may be involved, at least in part, in mediating the effects of beta-adrenergic agents in the mammalian heart.

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“…Some results have been published on the levels of P-LC phosphorylation in perfused heart that are not in agreement with those given above. Thus Kopp & Barany (1979) and Resink et al (1981a, b) both found low levels of phosphorylation in control perfusions (0.07-0.1 mol phosphate per mole of P-LC), and increases of 1.5 to 3-fold after several minutes with catecholamine. The reasons for the discrepancies are not obvious.…”

Section: P J Englandmentioning

confidence: 87%

Cardiac function and phosphorylation of contractile proteins

1983

Phil. Trans. R. Soc. Lond. B

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The primary regulation of cardiac contractility is probably through changes in the level of cytoplasmic free Ca 2+ . In the stimulation of contraction by catecholamines, secondary controls may be present at the level of the contractile proteins. Troponin-I, a subunit of the troponin complex of the thin filament, and C-protein, a thick filament component, are both phosphorylated in perfused hearts in response to catecholamines over time courses similar to that for the increase in contraction. Both proteins are also phosphorylated rapidly in vitro by cyclic-AMP-dependent protein kinase. Phosphorylation of troponin-I causes a decrease in the sensitivity of both cardiac myofibrillar ATPase and tension development of skinned fibre preparations to Ca 2+ , and also an increase in the rate of dissociation of Ca 2+ from isolated troponin. These results support the hypothesis that the role of phosphorylation of cardiac troponin-I is to contribute to the increased rate of relaxation of the heart that is observed with catecholamines. C-protein is phosphorylated to a maximum of 4-5 mol phosphate per mole protein both in vivo and in vitro . At present, however, the functions of both C-protein itself and its phosphorylation are unknown. Dephosphorylation of these contractile proteins after catecholamine stimulation is slow in perfused heart, although the rate can be increased by cholinergic agents. Phosphorylase, in contrast, is rapidly dephosphorylated under these circumstances. Phosphoprotein phosphatases relatively specific for phosphorylase have been identified in rat heart, whereas troponin-I appears to be dephosphorylated by general phosphatases. These observations account for the different rates of dephosphorylation of phosphorylase and the contractile proteins, but do not explain the slow dephosphorylation of the latter. In control perfused hearts myosin P-light chain was 50 % phosphorylated, and this was not changed by perfusion with positive inotropic agents or by short-term ischaemia. It was also unchanged during long-term hormonal modifications. Perfusions with 32 P 1 in rat heart give a half-time for the turnover of phosphate bound to the P-light chain of 2-4 min, showing that the myosin light chain kinase and phosphatase are active in the heart. It is hypothesized that under control conditions the kinase is already fully active, and that an increase in cytoplasmic Ca 2+ cannot therefore cause further activation of the enzyme.

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Phosphorylation of the 19,000-dalton light chain of myosin in perfused rat heart under the influence of negative and positive inotropic agents.

Cited by 90 publications

References 32 publications

Cardiovascular actions of lead and relationship to hypertension: a review.

Cardiovascular actions of lead and relationship to hypertension: a review.

Phosphorylation of phospholipids in isolated guinea pig hearts stimulated with isoprenaline

Cardiac function and phosphorylation of contractile proteins

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