Effects of carbachol and (−)‐N<sup>6</sup>‐phenylisopropyladenosine on myocardial inositol phosphate content and force of contraction

Kohl, Claudia; Linck, Bettina; Schmitz, Wilhelm; Scholz, Jens; Tóth, Mathias

doi:10.1111/j.1476-5381.1990.tb14165.x

Cited by 53 publications

(8 citation statements)

References 30 publications

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“…Activation of the A 1 R by the agonist R-(Ϫ)N 6 -(2-phenylisopropyl)-adenosine (PIA) has been reported to elevate inositol triphosphate levels in the myocardium (23). Others have reported, in avian ventricular myocytes, that the A 1 R agonist CCPA induces the accumulation of 1,2-diacylglycerol (DAG) and inositol phosphates, suggesting that the A 1 R is coupled to phospholipase C (PLC) (34).…”

mentioning

confidence: 98%

Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-ε to RACK2 in adult rat and mouse

Fenton¹,

Komatsu²,

Ikebe³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Adenosine protects the heart from adrenergic overstimulation. This adenoprotection includes the direct anti-adrenergic action via adenosine A(1) receptors (A(1)R) on the adrenergic signaling pathway. An indirect A(1)R-induced attenuation of adrenergic responsiveness involves the translocation of PKC-epsilon to t-tubules and Z-line of cardiomyocytes. We investigated with sarcomere imaging, immunocytochemistry imaging, and coimmunoprecipitation (co-IP) whether A(1)R activation of PKC-epsilon induces the kinase translocation to receptor for activated C kinase 2 (RACK2) in isolated rat and mouse hearts and whether phospholipase C (PLC) is involved. Rat cardiomyocytes were treated with the A(1)R agonist chlorocyclopentyladenosine (CCPA) and exposed to primary PKC-epsilon and RACK2 antibodies with secondaries conjugated to Cy3 and Cy5 (indodicarbocyanine), respectively. Scanning confocal microscopy showed that CCPA caused PKC-epsilon to reversibly colocalize with RACK2 within 3 min. Additionally, rat and mouse hearts were perfused and stimulated with CCPA or phenylisopropyladenosine to activate A(1)R, or with phorbol 12-myristate 13-acetate to activate PKC. RACK2 was immunoprecipitated from heart extracts and resolved with SDS-PAGE. Western blotting showed that CCPA, phenylisopropyladenosine, and phorbol 12-myristate 13-acetate in the rat heart increased the PKC-epsilon co-IP with RACK2 by 186, 49, and >1,000%, respectively. The A(1)R antagonist 8-cyclopentyl-1,3-dipropylxanthine prevented the CCPA-induced co-IP with RACK2. In mouse hearts, CCPA increased the co-IP of PKC-epsilon with RACK2 by 61%. With rat cardiomyocytes, the beta-adrenergic agonist isoproterenol increased sarcomere shortening by 177%. CCPA reduced this response by 47%, an action inhibited by the PLC inhibitor U-73122 and 8-cyclopentyl-1,3-dipropylxanthine. In conclusion, A(1)R stimulation of the heart is associated with PLC-initiated PKC-epsilon translocation and association with RACK2.

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mentioning

confidence: 98%

Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-ε to RACK2 in adult rat and mouse

Fenton¹,

Komatsu²,

Ikebe³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…In cardiac myocytes, the activation of several types of receptors, such as ␣ 1 -adrenergic (1)(2)(3)(4)(5), muscarinic (1,6), and purinergic (6) dynorphin A (7), endothelin-1 (8,9), and angiotensin II (10 -12) receptors, stimulates the hydrolysis of membrane phosphoinositides leading to the generation of two classes of second messengers, diacylglycerol and inositol trisphosphate. In many tissues diacylglycerol directly activates both the conventional Ca 2ϩ -dependent group of PKC 1 isozymes (␣, ␤ I , ␤ II , and ␥) and the novel Ca 2ϩ -independent group of PKC isozymes (␦, ⑀, , and ), whereas inositol trisphosphate, by increasing intracellular Ca 2ϩ , indirectly activates Ca 2ϩ -dependent PKC isozymes (for a review, see Ref.…”

Section: Sensitivity Respectively Of Actomyosin S-1 Mgatpasementioning

confidence: 99%

Cardiac Troponin I Mutants

Noland

Guo

Raynor

et al. 1995

Journal of Biological Chemistry

157

173

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2؉sensitivity of the myofilament.It is suggested that Ser-43/Ser-45 and Ser-23/Ser-24 in cardiac TnI are important for normal Ca 2؉ sensitivity of the myofilament, and that phosphorylation of Ser-43/ Ser-45 and Ser-23/Ser-24 is primarily involved in the protein kinase C regulation of the activity and Ca 2؉ sensitivity, respectively, of actomyosin S-1 MgATPase.In cardiac myocytes, the activation of several types of receptors, such as ␣ 1 -adrenergic (1-5), muscarinic (1, 6), and purinergic (6) dynorphin A (7), endothelin-1 (8, 9), and angiotensin (14 -18). However, the complex molecular events mediated by PKC (or more precisely, by the individual isozymes) that are responsible for cardiac contractility regulation, for example, remain largely unclear. It has been reported that phenylephrine (␣ 1 -adrenergic receptor agonist) elicited transient negative inotropy followed by sustained positive inotropy (3, 19 -21), endothelin-1 caused monotonic positive inotropy (22), whereas dynorphin A (-opioid receptor agonist) induced negative inotropy (7). All three of these distinct receptor agonists are believed to act, at least in part, through PKC activation. Furthermore, phorbol esters (such as TPA), potent and long-acting PKC activators, produced predominantly negative inotropic effects in various cardiac preparations (23-27). These seemingly paradoxical observations might reflect certain opposing factors of PKC activation which include the net effects of intracellular pH change, the size of intracellular Ca 2ϩ transient, and the states and species of cellular proteins being phosphorylated.One target for PKC in the heart is the contractile apparatus itself. Cardiac TnI and TnT from the thin filament have been shown to be effective substrates for PKC (28), and some of the phosphorylation sites in these proteins have been determined (29,30). Phosphorylation of TnI and/or TnT by PKC resulted in an inhibition of Ca 2ϩ -stimulated MgATPase of the reconstituted actomyosin complex (31-33) or in native myofibril preparations (32, 34), an effect associated with altered interactions among the contractile protein components (32,33). PKC also phosphorylated MLC2 (34 -36) and C-protein (34 -36) in myofibrillar and thick filament preparations. Phosphorylation of

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“…Adenosine is reported to increase the content of inositol 1,4,5-trisphosphate through increases in diacylglycerol (24), suggesting that protein kinase C may deactivate ectosolic and cytosolic 5 '-nucleotidase. However, we have preliminarily reported that protein kinase C rather activates 5 '-nucleotidase in rat cardiomyocytes (25 5 '-nucleotidase is not the sole determinant of adenosine release.…”

Section: Resultsmentioning

confidence: 99%

Evidence for deactivation of both ectosolic and cytosolic 5'-nucleotidase by adenosine A1 receptor activation in the rat cardiomyocytes.

Kitakaze¹,

Hori²,

Minamino³

et al. 1994

J. Clin. Invest.

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Adenosine, an important regulator of many cardiac functions, is produced by ectosolic and cytosolic 5 '-nucleotidase. The activity of these enzymes is influenced by several ischemia-sensitive metabolic factors, e.g., ATP, ADP, H+, and inorganic phosphate. However, there is no clear evidence that adenosine itself affects 5'-nucleotidase activity. This study tested whether adenosine decreases the activity of ectosolic and cytosolic 5 '-nucleotidase. Cardiomyocytes were isolated from adult male Wistar rats and suspended in the modified Hepes-Tyrode buffer solution. After stabilization, isolated cardiomyocytes were incubated with and without adenosine (10-9-i0-' M). .05] at 10-6 M adenosine) after 30 min. The decrease in ectosolic and cytosolic 5 '-nucleotidase activity was inhibited by 8-phenyltheophylline and pertussis toxin, and was mimicked by N6-cyclohexyladenosine, an adenosine Al receptor agonist. Neither CGS21680C, and A2 receptor agonist, nor cycloheximide deactivated ectosolic and cytosolic 5 '-nucleotidase. Thus, we conclude that activation of adenosine A1 receptors is coupled to G; proteins and attenuates ectosolic and cytosolic 5 '-nucleotidase activity in rat cardiomyocytes.

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Effects of carbachol and (−)‐N⁶‐phenylisopropyladenosine on myocardial inositol phosphate content and force of contraction

Cited by 53 publications

References 30 publications

Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-ε to RACK2 in adult rat and mouse

Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-ε to RACK2 in adult rat and mouse

Cardiac Troponin I Mutants

Evidence for deactivation of both ectosolic and cytosolic 5'-nucleotidase by adenosine A1 receptor activation in the rat cardiomyocytes.

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Effects of carbachol and (−)‐N6‐phenylisopropyladenosine on myocardial inositol phosphate content and force of contraction

Cited by 53 publications

References 30 publications

Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-ε to RACK2 in adult rat and mouse

Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-ε to RACK2 in adult rat and mouse

Cardiac Troponin I Mutants

Evidence for deactivation of both ectosolic and cytosolic 5'-nucleotidase by adenosine A1 receptor activation in the rat cardiomyocytes.

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Effects of carbachol and (−)‐N⁶‐phenylisopropyladenosine on myocardial inositol phosphate content and force of contraction