Pharmacological profile of the ATP‐mediated increase in L‐type calcium current amplitude and activation of a non‐specific cationic current in rat ventricular cells

Scamps, Frédérique; Vassort, Guy

doi:10.1111/j.1476-5381.1994.tb17089.x

Cited by 40 publications

(41 citation statements)

References 32 publications

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“…3). Moreover, ATP-dependent calcium influx was reportedly blocked by suramin (19), whereas the effect of the nucleotide on glucose transport was not influenced by this antagonist (Fig. 2).…”

Section: Discussionmentioning

confidence: 84%

Purinergic Inhibition of Glucose Transport in Cardiomyocytes

Fischer¹,

Becker²,

Löken³

1999

Journal of Biological Chemistry

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ATP is known to act as an extracellular signal in many organs. In the heart, extracellular ATP modulates ionic processes and contractile function. This study describes a novel, metabolic effect of exogenous ATP in isolated rat cardiomyocytes. In these quiescent (i.e. noncontracting) cells, micromolar concentrations of ATP depressed the rate of basal, catecholamine-stimulated, or insulinstimulated glucose transport by up to 60% (IC 50 for inhibition of insulin-dependent glucose transport, 4 M). ATP decreased the amount of glucose transporters (GLUT1 and GLUT4) in the plasma membrane, with a concomitant increase in intracellular microsomal membranes. A similar glucose transport inhibition was produced by P 2 purinergic agonists with the following rank of potencies: ATP Ϸ ATP␥S Ϸ 2-methylthio-ATP (P 2Y -selective) > ADP > ␣,␤meATP (P 2X -selective), whereas the P 1 purinoceptor agonist adenosine was ineffective. The effect of ATP was suppressed by the poorly subtypeselective P 2 antagonist pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid but, surprisingly, not by the nonselective antagonist suramin nor by the P 2Y -specific Reactive Blue 2. Glucose transport inhibition by ATP was not affected by a drastic reduction of the extracellular concentrations of calcium (down to 10 ؊9 M) or sodium (down to 0 mM), and it was not mimicked by a potassium-induced depolarization, indicating that purinoceptors of the P 2X family (which are nonselective cation channels whose activation leads to a depolarizing sodium and calcium influx) are not involved. Inhibition was specific for the transmembrane transport of glucose because ATP did not inhibit (i) the rate of glycolysis under conditions where the transport step is no longer rate-limiting nor (ii) the rate of [1-14 C]pyruvate decarboxylation. In conclusion, extracellular ATP markedly inhibits glucose transport in rat cardiomyocytes by promoting a redistribution of glucose transporters from the cell surface to an intracellular compartment. This effect of ATP is mediated by P 2 purinoceptors, possibly by a yet unknown subtype of the P 2Y purinoceptor family.It is well established that ATP acts as an extracellular signal in many tissues and is involved in a variety of regulatory processes including the control of vascular tone, muscle contraction, pain, or neuronal communication (for review see Ref.1). In particular, ATP serves as a neurotransmitter or cotransmitter in central, as well as in peripheral neurons (1, 2). For instance, ATP is co-released with noradrenaline or acetylcholine from sympathetic or parasympathetic nerve endings, respectively, and even from neuromuscular synapses (1). Another source of extracellular ATP is that released from parenchymal cells under hypoxic or ischemic conditions (3).Many biological responses to ATP are mediated via P 2 purinoceptors, which belong to either of two structurally and functionally distinct families of receptors: ligand-gated, nonselective cation channels (P 2X -type), or G-protein-coupled receptors linked to the phospholipase C...

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Section: Discussionmentioning

confidence: 84%

Purinergic Inhibition of Glucose Transport in Cardiomyocytes

Fischer¹,

Becker²,

Löken³

1999

Journal of Biological Chemistry

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“…Using a train protocol to measure the rate of block of the Ltype Ca21 channel current (Kass & Arena, 1989) previously reported on atrial and ventricular preparations in the literature (which occurred within several minutes instead of seconds) (Alvarez et al, 1990;Qu et al, 1993 washout on the sinus node activity has been reported in only one study on the isolated, spontaneously beating guinea-pig heart preparation (Stark et al, 1993), whereas in other reported studies the [ATP]O-induced effect disappeared gradually (3-5 min) following washout (Alvarez et al, 1990;Scamps et al, 1992;Qu et al, 1993;Scamps & Vassort, 1994 (Scamps et al, 1992;Qu et al, 1993). In order to investigate the type(s) of purinoceptor involved in our present study, different commercially available purinoceptor antagonists were examined.…”

Section: Discussionmentioning

confidence: 91%

“…Most studies in the literature examining the modulatory effects of [ATP]o on L-type Ca2+ channel currents have used myocytes isolated from atria and ventricles (Alvarez et al, 1990;Qu et al, 1992;Mantelli et al, 1993;Scamps et al, 1992;Scamps & Vassort, 1994) and both an increase and a decrease in the L-type Ca21 channel current amplitude, has been reported. Unlike the atrial and ventricular myocardia, in the SAN the L-type Ca2+ channel current has been suggested to play an important role in the initiation of the action potential (Irisawa & Noma, 1984, Doerr et al, 1989 1 Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

Modulation by extracellular ATP of L‐type calcium channels in guinea‐pig single sinoatrial nodal cell

Kwan

1996

British J Pharmacology

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“…For adult skeletal muscle, ATP has been found to facilitate acetylcholine stimulation via an unidentified second messenger pathway (21) and in rat diaphragm ATP␥S increases inositol phosphate formation (22). For cardiac myocytes, while some ATP-induced cationic currents seen there may be due to P2X purinoceptors, the positive inotropic effects of ATP and its potent ability to increase calcium transients in stimulated rat heart and to increase the L-type calcium current in cardiac myocytes have been attributed to metabotropic (P2Y) purinoceptors (23)(24)(25)(26). ATP was found to be active on ventricular myocytes with EC 50 ϳ300 nM and 2-MeSATP and ATP␥S were similarly highly potent (24).…”

Section: Analysis Of the P2ymentioning

confidence: 99%

Molecular Cloning of a Novel P2 Purinoceptor from Human Erythroleukemia Cells

Akbar

Dasari

Webb

et al. 1996

Journal of Biological Chemistry

122

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Screening of a human erythroleukemia cell cDNA library with radiolabeled chicken P2Y 3 cDNA at low stringency revealed a cDNA clone encoding a novel G protein-coupled receptor with homology to P2 purinoceptors. This receptor, designated P2Y 7 , has 352 amino acids and shares 23-30% amino acid identity with the P2Y 1 -P2Y 6 purinoceptors. The P2Y 7 cDNA was transiently expressed in COS-7 cells: binding studies thereon showed a very high affinity for ATP (37 ؎ 6 nM), much less for UTP and ADP (ϳ1300 nM), and a novel rank order of affinities in the binding series studied of 8 nucleotides and suramin. The P2Y 7 receptor sequence appears to denote a different subfamily from that of all the other known P2Y purinoceptors, with only a few of their characteristic sequence motifs shared. The P2Y 7 receptor mRNA is abundantly present in the human heart and the skeletal muscle, moderately in the brain and liver, but not in the other tissues tested. The P2Y 7 receptor mRNA was also abundantly present in the rat heart and cultured neonatal rat cardiomyocytes. The P2Y 7 receptor is functionally coupled to phospholipase C in COS-7 cells transiently expressing this receptor. The P2Y 7 gene was shown to be localized to human chromosome 14. We have thus cloned a unique member of the P2Y purinoceptor family which probably plays a role in the regulation of cardiac muscle contraction.The widespread occurrence of metabotropic receptors for extracellular ATP has long been inferred from physiological and pharmacological evidence (1). A number of such G proteincoupled ATP receptors have been characterized and a consensus on their nomenclature has termed all of these as P2Y purinoceptors (to be individually named P2Y 1 to P2Y n ), regardless of previous terminology such as P 2U or P 2T for subclasses thereof (2). The first such receptors to be characterized by DNA cloning and expression were the P2Y 1 receptor (where UTP is inactive) (3) and the P2Y 2 receptor (ATP and UTP are equally active) (4). True species homologues (or orthologues) of P2Y 1 have since been obtained, e.g. bovine (5) and human (6), and of P2Y 2 , e.g. from human airway epithelium (7) or human erythroleukemia (HEL) 1 cells (8). Further types identified by cloning have been the P2Y 3 receptor (UDP Ͼ ADP Ͼ ATP) (9) and P2Y 4 (UTP Ͼ Ͼ ATP, and more strongly related to P2Y 2 ) (10, 11). Further novel P2Y receptors have recently been identified from their cDNAs from chicken activated T lymphocytes (12) and rat vascular smooth muscle cells (13) and designated P2Y 5 and P2Y 6 receptors. Previously we have demonstrated at least three P2 purinoceptors on the hematopoietic cell line, HEL cells, by intracellular calcium mobilization and by photoaffinity labeling (8). Here we report the molecular cloning and characterization of one of these, a novel P2 purinergic receptor designated P2Y 7 .

show abstract

Pharmacological profile of the ATP‐mediated increase in L‐type calcium current amplitude and activation of a non‐specific cationic current in rat ventricular cells

Cited by 40 publications

References 32 publications

Purinergic Inhibition of Glucose Transport in Cardiomyocytes

Purinergic Inhibition of Glucose Transport in Cardiomyocytes

Modulation by extracellular ATP of L‐type calcium channels in guinea‐pig single sinoatrial nodal cell

Molecular Cloning of a Novel P2 Purinoceptor from Human Erythroleukemia Cells

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