Phosphorylation of phospholipids in isolated guinea pig hearts stimulated with isoprenaline

Jakab, G; Rapundalo, Stephen T.; Solaro, R. John; Kranias, Evangelia G.

doi:10.1042/bj2510189

Cited by 9 publications

(6 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Figure 4D shows the responses obtained for strong activation of cardiac ␤-receptors by 0.5 M isoproteronol for 10 min, which, on the basis of visual inspection, induced large increases of contraction magnitude and frequency. In contrast to a previous report (33), PIP 2 did not change in guinea pig ventricles, whereas PIP increased significantly by 19%. Similar experiments with guinea pig atria generated very similar results (data not shown).…”

Section: Determinants Of Pip 2 In Cardiac Sarcolemma: Impressions Frocontrasting

confidence: 54%

“…In superfused right ventricular strips from rat, strong ␣-adrenergic stimulation results in a modest decrease of PIP 2 with a smaller rebound in a few minutes; during a rapid train of electrical stimuli, IP 3 levels rise by about 30% whereas PIP 2 levels do not change (53). In addition to these reports, it has been suggested that PIP 2 levels may increase during ␤-adrenergic stimulation in intact cardiac tissue (13,33).…”

mentioning

confidence: 86%

See 1 more Smart Citation

Modulation of cardiac PIP₂ by cardioactive hormones and other physiologically relevant interventions

Nasuhoglu¹,

Feng²,

Mao³

et al. 2002

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

5-bisphosphate (PIP 2) affects profoundly several cardiac ion channels and transporters, and studies of PIP2-sensitive currents in excised patches suggest that PIP 2 can be synthesized and broken down within 30 s. To test when, and if, total phosphatidylinositol 4-phosphate (PIP) and PIP2 levels actually change in intact heart, we used a new, nonradioactive HPLC method to quantify anionic phospholipids. Total PIP and PIP2 levels (10-30 mol/kg wet weight) do not change, or even increase, with activation of G␣ q/phospholipase C (PLC)-dependent pathways by carbachol (50 M), phenylephrine (50 M), and endothelin-1 (0.3 M). Adenosine (0.2 mM) and phorbol 12-myristate 13-acetate (1M) both cause 30% reduction of PIP2 in ventricles, suggesting that diacylglycerol (DAG)-dependent mechanisms negatively regulate cardiac PIP2. PIP2, but not PIP, increases reversibly by 30% during electrical stimulation (2 Hz for 5 min) in guinea pig left atria; the increase is blocked by nickel (2 mM). Both PIP and PIP2 increase within 3 min in hypertonic solutions, roughly in proportion to osmolarity, and similar effects occur in multiple cell lines. Inhibitors of several volume-sensitive signaling mechanisms do not affect these responses, suggesting that PIP2 metabolism might be sensitive to membrane tension, per se. phosphatidylinositol 4,5-bisphosphate; phosphatidylinositol; diacylglycerol; phorbol ester; cardiac muscle; G protein-coupled receptors; phospholipase C; cell volume PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE (PIP 2 ) is the phospholipid precursor of three second messengers, D-myo-inositol 1,4,5-trisphosphate (IP 3 ), diacylglycerol (DAG), and phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) (66). At the same time, PIP 2 serves other cellular functions. It anchors and modulates the function of numerous cell signaling proteins and cytoskeleton at the cell membrane (11,17,42,65), including at least one transcription factor that is released by phospholipase C (PLC) activation (60). In addition, PIP 2 metabolism is coupled to membrane trafficking, including some forms of exo-and endocytosis (7, 46). Finally, PIP 2 modulates the function of phospholipases (14), receptor kinases (16, 52), and ion transporters and ion channels (25). Especially, the anchoring/recruitment functions and the modulatory functions of PIP 2 beg the question as to how, and if, PIP 2 might be used as a cell signal. For cardiac physiology, an answer to this question seems especially important at this time, because sarcolemmal mechanisms that affect both cardiac contraction (e.g., Na ϩ /Ca 2ϩ exchange) and contraction frequency [e.g., G protein-coupled inwardly rectifying K ϩ (GIRK) channels] are strongly PIP 2 dependent (27).The minimum biochemical mechanisms involved in cardiac myocyte PIP 2 metabolism (39) are summarized in Fig. 1. The dominant pathway of PIP 2 synthesis, as in other cells, is probably the sequential phosphorylation in the sarcolemma of phosphatidylinositol (PI) at the 4-and then the 5-positions of inositol (66). As in other cells, PIP 2 is hydr...

show abstract

Section: Determinants Of Pip 2 In Cardiac Sarcolemma: Impressions Frocontrasting

confidence: 54%

mentioning

confidence: 86%

Modulation of cardiac PIP₂ by cardioactive hormones and other physiologically relevant interventions

Nasuhoglu¹,

Feng²,

Mao³

et al. 2002

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…Increased 32 P incorporation into phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4,5-diphosphate (PIP 2 ) was found in perfused guinea pig hearts subjected to /3-adrenergic stimulation. 13 These rapid changes in the amounts of polyphosphoinositides have been proposed to be involved in mediating, at least in part, the effects of /3-adrenergic agents. 13 However, there are no data on the mechanism by which activation of the /3-receptor is associated with increased formation of polyphosphoinositides in the mammalian myocardium.…”

mentioning

confidence: 99%

“…13 These rapid changes in the amounts of polyphosphoinositides have been proposed to be involved in mediating, at least in part, the effects of /3-adrenergic agents. 13 However, there are no data on the mechanism by which activation of the /3-receptor is associated with increased formation of polyphosphoinositides in the mammalian myocardium.…”

mentioning

confidence: 99%

“…Thus, the response of heart cells to /3-adrenergic stimulation is likely to involve coordinated changes in the extent of cAMPdependent phosphorylation of several regulatory proteins. However, besides protein phosphorylation, the phosphorylation of a special class of phospholipids (polyphosphoinositides) has also been shown to occur as a result of activation of cAMPdependent protein kinase under in vitro 9 - 12 and in vivo 13 conditions. Increased 32 P incorporation into phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4,5-diphosphate (PIP 2 ) was found in perfused guinea pig hearts subjected to /3-adrenergic stimulation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Changes in phosphoinositide turnover in isolated guinea pig hearts stimulated with isoproterenol.

Édes

Solaro

Kranias

1989

Circulation Research

Self Cite

View full text Add to dashboard Cite

The incorporation of 32 P, into phospholamban, troponin I, phosphatidylinositols, and inositol trisphosphates was studied in Langendorff-perfused guinea pig hearts stimulated with isoproterenol. Hearts were perfused with Krebs-Henseleit buffer containing [ 32 P]P| and freezeclamped at different times during the positive inotropic response. Exposure of the hearts to 0.1 /AM isoproterenol for up to 1 minute was associated with significant (up to threefold) increases in phospholamban and troponin I phosphorylation, but there was no significant increase in 32 P incorporation into phospholipids. However, longer exposure (2 minutes or more) to isoproterenol was associated with increases in the degree of P labeling of phosphatidylinositols and phosphatidic acid. Examination of 32 P labeling of Inositol trisphosphates in the same hearts revealed that the radioactivity associated with these compounds decreased with time. The decreases were significant at times of exposure of 2 minutes or longer to 0-adrenergic stimulation. The tissue levels of the inositol 1,4,5-trisphosphate isoform were also measured in hearts perfused with isoproterenol for 3 minutes, and they were found to be significantly lower compared with values obtained in control hearts. The effects of isoproterenol on 32 P incorporation into phospholipids and proteins were observed in the presence of prazosin, and they were completely abolished by the /3-receptor blocker propranolol. Examination of the phosphoinositldespecific phosphoUpase C activity in the perfused hearts revealed that isoproterenol stimulation was associated with a decrease in the membrane-associated enzymatic activity at physiological calcium concentrations. These findings indicate that 0-adrenergic stimulation of isolated hearts is associated with changes in basal phosphatidylinositol turnover that may be mediated, at least in part, by inhibition of the phosphoUpase C enzymatic activity specific for phosphatidylinositols. Received December 28, 1988; accepted April 25, 1989. myofibrils, the sites of phosphorylation are troponin I and C protein, 1 -2 and the increased phosphate incorporation into these proteins is associated with a decrease in the Ca 2+ sensitivity of the myofibrillar Mg 2+ -dependent ATPase activity. 1 ' 3 The site of phosphorylation in SR, due to ^-agonist stimulation, has been shown to be on phospholamban, and stimulation of phosphate incorporation results in increased rates of calcium transport by the SR.1 -4 Dephosphorylation of phospholamban occurs on reversal of the mechanical effects of isoproterenol, 2 and this is probably mediated by protein phosphatases associated with cardiac SR membranes.5 /3-Adrenergic stimulation has also been shown to result in phosphorylation of a 15 kDa protein in sarcolemma, which may be involved in increasing transsarcolemmal calcium flux through the slow inward Ca 2+ channels.6 -7 The activation of glycogenolysis and inactivation of grycogen synthesis are also synchronously controlled by cAMP-dependent phosphorylation 8 to cover energ...

show abstract

Occurrence and Functions of the Phosphatidylinositol Cycle in the Myocardium

Lamers

Dekkers

Bezstarosti

et al. 1992

Lipid Metabolism in the Healthy and Disease Heart

View full text Add to dashboard Cite

Phosphorylation of phospholipids in isolated guinea pig hearts stimulated with isoprenaline

Cited by 9 publications

References 33 publications

Modulation of cardiac PIP₂ by cardioactive hormones and other physiologically relevant interventions

Modulation of cardiac PIP₂ by cardioactive hormones and other physiologically relevant interventions

Changes in phosphoinositide turnover in isolated guinea pig hearts stimulated with isoproterenol.

Occurrence and Functions of the Phosphatidylinositol Cycle in the Myocardium

Contact Info

Product

Resources

About

Phosphorylation of phospholipids in isolated guinea pig hearts stimulated with isoprenaline

Cited by 9 publications

References 33 publications

Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions

Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions

Changes in phosphoinositide turnover in isolated guinea pig hearts stimulated with isoproterenol.

Occurrence and Functions of the Phosphatidylinositol Cycle in the Myocardium

Contact Info

Product

Resources

About

Modulation of cardiac PIP₂ by cardioactive hormones and other physiologically relevant interventions

Modulation of cardiac PIP₂ by cardioactive hormones and other physiologically relevant interventions