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Potentiation of P2Y receptors by physiological elevations of extracellular K+ via a mechanism independent of Ca2+ influx.

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Potentiation of P2Y receptors by physiological elevations of extracellular K+ via a mechanism independent of Ca2+ influx. / Pitt, Samantha Jane; Martinez-Pinna, Juan; Barnard, Eric A; Mahaut-Smith, Martyn P.

In: Molecular Pharmacology, Vol. 67, No. 5, 2005, p. 1705-13.

Research output: Contribution to journalArticlepeer-review

Harvard

Pitt, SJ, Martinez-Pinna, J, Barnard, EA & Mahaut-Smith, MP 2005, 'Potentiation of P2Y receptors by physiological elevations of extracellular K+ via a mechanism independent of Ca2+ influx.', Molecular Pharmacology, vol. 67, no. 5, pp. 1705-13. https://doi.org/10.1124/mol.104.009902

APA

Pitt, S. J., Martinez-Pinna, J., Barnard, E. A., & Mahaut-Smith, M. P. (2005). Potentiation of P2Y receptors by physiological elevations of extracellular K+ via a mechanism independent of Ca2+ influx. Molecular Pharmacology, 67(5), 1705-13. https://doi.org/10.1124/mol.104.009902

Vancouver

Pitt SJ, Martinez-Pinna J, Barnard EA, Mahaut-Smith MP. Potentiation of P2Y receptors by physiological elevations of extracellular K+ via a mechanism independent of Ca2+ influx. Molecular Pharmacology. 2005;67(5):1705-13. https://doi.org/10.1124/mol.104.009902

Author

Pitt, Samantha Jane ; Martinez-Pinna, Juan ; Barnard, Eric A ; Mahaut-Smith, Martyn P. / Potentiation of P2Y receptors by physiological elevations of extracellular K+ via a mechanism independent of Ca2+ influx. In: Molecular Pharmacology. 2005 ; Vol. 67, No. 5. pp. 1705-13.

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@article{83808ecefdf742d1b988e6efb70c2de0,
title = "Potentiation of P2Y receptors by physiological elevations of extracellular K+ via a mechanism independent of Ca2+ influx.",
abstract = "Many physiological and pathophysiological situations generate a significant increase in extracellular K+ concentration. This is known to influence a number of membrane conductances and exchangers, whereas direct effects of K+ on the activation of G protein-coupled receptors have not been reported. We now show that Ca2+ release evoked by P2Y1 receptors expressed in 1321-N1 astrocytoma cells is markedly potentiated by small increases in external K+ concentration. This effect was blocked by the phospholipase-C inhibitor U-73122 (1-[6-[[17 beta]-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione), but not by its analog U-73343 (1-[6-[[17 beta]-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrrolidinedione), and not by nifedipine, Ni2+, Cd2+, or Gd3+. Thus, K+ enhances d-myo-inositol 1,4,5-trisphosphate-dependent Ca2+ release without a requirement for Ca2+ influx. The cation dependence of this effect displayed the order K+ > Rb+ > N-methyl-D-glucamine+, and Cs+ and choline+ were ineffective. The potentiation by K+ is half-maximal at an increase of 2.6 mM (total K+ of 7.6 mM). K+ caused a reduction in EC50 (2.7-fold for a 29 mM increase) without a change of slope; thus, the greatest effect was observed at near-threshold agonist levels. The response to K+ can be explained in part by depolarization-dependent potentiation of P2Y1 receptors [J Physiol (Lond) 555:61-70, 2004]. However, electrophysiological recordings of 1321-N1 cells and megakaryocytes demonstrated that K+ also amplifies ADP-evoked Ca2+ responses independently of changes in membrane potential. Elevated K+ also amplified endogenous UTP-dependent Ca2+ responses in human embryonic kidney 293 cells, suggesting that other P2Y receptors are K(+)-dependent. P2Y receptors display a widespread tissue distribution; therefore, their modulation by small changes in extracellular K+ may represent a novel means of autocrine and paracrine regulation of cellular activity.",
keywords = "P2 receptors, Purine Nucleotides, Platelets, Hemostasis",
author = "Pitt, {Samantha Jane} and Juan Martinez-Pinna and Barnard, {Eric A} and Mahaut-Smith, {Martyn P}",
year = "2005",
doi = "10.1124/mol.104.009902",
language = "English",
volume = "67",
pages = "1705--13",
journal = "Molecular Pharmacology",
issn = "1521-0111",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "5",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Potentiation of P2Y receptors by physiological elevations of extracellular K+ via a mechanism independent of Ca2+ influx.

AU - Pitt, Samantha Jane

AU - Martinez-Pinna, Juan

AU - Barnard, Eric A

AU - Mahaut-Smith, Martyn P

PY - 2005

Y1 - 2005

N2 - Many physiological and pathophysiological situations generate a significant increase in extracellular K+ concentration. This is known to influence a number of membrane conductances and exchangers, whereas direct effects of K+ on the activation of G protein-coupled receptors have not been reported. We now show that Ca2+ release evoked by P2Y1 receptors expressed in 1321-N1 astrocytoma cells is markedly potentiated by small increases in external K+ concentration. This effect was blocked by the phospholipase-C inhibitor U-73122 (1-[6-[[17 beta]-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione), but not by its analog U-73343 (1-[6-[[17 beta]-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrrolidinedione), and not by nifedipine, Ni2+, Cd2+, or Gd3+. Thus, K+ enhances d-myo-inositol 1,4,5-trisphosphate-dependent Ca2+ release without a requirement for Ca2+ influx. The cation dependence of this effect displayed the order K+ > Rb+ > N-methyl-D-glucamine+, and Cs+ and choline+ were ineffective. The potentiation by K+ is half-maximal at an increase of 2.6 mM (total K+ of 7.6 mM). K+ caused a reduction in EC50 (2.7-fold for a 29 mM increase) without a change of slope; thus, the greatest effect was observed at near-threshold agonist levels. The response to K+ can be explained in part by depolarization-dependent potentiation of P2Y1 receptors [J Physiol (Lond) 555:61-70, 2004]. However, electrophysiological recordings of 1321-N1 cells and megakaryocytes demonstrated that K+ also amplifies ADP-evoked Ca2+ responses independently of changes in membrane potential. Elevated K+ also amplified endogenous UTP-dependent Ca2+ responses in human embryonic kidney 293 cells, suggesting that other P2Y receptors are K(+)-dependent. P2Y receptors display a widespread tissue distribution; therefore, their modulation by small changes in extracellular K+ may represent a novel means of autocrine and paracrine regulation of cellular activity.

AB - Many physiological and pathophysiological situations generate a significant increase in extracellular K+ concentration. This is known to influence a number of membrane conductances and exchangers, whereas direct effects of K+ on the activation of G protein-coupled receptors have not been reported. We now show that Ca2+ release evoked by P2Y1 receptors expressed in 1321-N1 astrocytoma cells is markedly potentiated by small increases in external K+ concentration. This effect was blocked by the phospholipase-C inhibitor U-73122 (1-[6-[[17 beta]-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione), but not by its analog U-73343 (1-[6-[[17 beta]-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrrolidinedione), and not by nifedipine, Ni2+, Cd2+, or Gd3+. Thus, K+ enhances d-myo-inositol 1,4,5-trisphosphate-dependent Ca2+ release without a requirement for Ca2+ influx. The cation dependence of this effect displayed the order K+ > Rb+ > N-methyl-D-glucamine+, and Cs+ and choline+ were ineffective. The potentiation by K+ is half-maximal at an increase of 2.6 mM (total K+ of 7.6 mM). K+ caused a reduction in EC50 (2.7-fold for a 29 mM increase) without a change of slope; thus, the greatest effect was observed at near-threshold agonist levels. The response to K+ can be explained in part by depolarization-dependent potentiation of P2Y1 receptors [J Physiol (Lond) 555:61-70, 2004]. However, electrophysiological recordings of 1321-N1 cells and megakaryocytes demonstrated that K+ also amplifies ADP-evoked Ca2+ responses independently of changes in membrane potential. Elevated K+ also amplified endogenous UTP-dependent Ca2+ responses in human embryonic kidney 293 cells, suggesting that other P2Y receptors are K(+)-dependent. P2Y receptors display a widespread tissue distribution; therefore, their modulation by small changes in extracellular K+ may represent a novel means of autocrine and paracrine regulation of cellular activity.

KW - P2 receptors

KW - Purine Nucleotides

KW - Platelets

KW - Hemostasis

UR - http://molpharm.aspetjournals.org/content/67/5/1705.full.pdf+html

U2 - 10.1124/mol.104.009902

DO - 10.1124/mol.104.009902

M3 - Article

VL - 67

SP - 1705

EP - 1713

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 1521-0111

IS - 5

ER -

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