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Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).

Publication ,  Journal Article
Kilts, JD; Gerhardt, MA; Richardson, MD; Sreeram, G; Mackensen, GB; Grocott, HP; White, WD; Davis, RD; Newman, MF; Reves, JG; Schwinn, DA; Kwatra, MM
Published in: Circ Res
October 13, 2000

Cardiac G protein-coupled receptors that couple to Galpha(s) and stimulate cAMP formation (eg, beta-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have revealed that one of these receptors, the beta(2)-adrenergic receptor (AR), also couples to the inhibitory G protein Galpha(i) (activation of which inhibits cAMP formation). If beta(2)ARs could be shown to couple to Galpha(i) in the human heart, it would have important ramifications, because levels of Galpha(i) increase with age and in failing human heart. Therefore, we investigated whether beta(2)ARs in the human heart activate Galpha(i). By photoaffinity labeling human atrial membranes with [(32)P]azidoanilido-GTP, followed by immunoprecipitation with antibodies specific for Galpha(i), we found that Galpha(i) is activated by stimulation of beta(2)ARs but not of beta(1)ARs. In addition, we found that other Galpha(s)-coupled receptors also couple to Galpha(i), including histamine, serotonin, and glucagon. When coupling of these receptors to Galpha(i) is disrupted by pertussis toxin, their ability to stimulate adenylyl cyclase is enhanced. These data provide the first evidence that beta(2)AR and many other Galpha(s)-coupled receptors in human atrium also couple to Galpha(i) and that abolishing the coupling of these receptors to Galpha(i) increases the receptor-mediated adenylyl cyclase activity.

Duke Scholars

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

October 13, 2000

Volume

87

Issue

8

Start / End Page

705 / 709

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Signal Transduction
  • Receptors, Serotonin
  • Receptors, Histamine
  • Receptors, Glucagon
  • Receptors, Cell Surface
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-1
  • Precipitin Tests
  • Photoaffinity Labels
 

Citation

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MLA
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Kilts, J. D., Gerhardt, M. A., Richardson, M. D., Sreeram, G., Mackensen, G. B., Grocott, H. P., … Kwatra, M. M. (2000). Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i). Circ Res, 87(8), 705–709. https://doi.org/10.1161/01.res.87.8.705
Kilts, J. D., M. A. Gerhardt, M. D. Richardson, G. Sreeram, G. B. Mackensen, H. P. Grocott, W. D. White, et al. “Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).Circ Res 87, no. 8 (October 13, 2000): 705–9. https://doi.org/10.1161/01.res.87.8.705.
Kilts JD, Gerhardt MA, Richardson MD, Sreeram G, Mackensen GB, Grocott HP, et al. Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i). Circ Res. 2000 Oct 13;87(8):705–9.
Kilts, J. D., et al. “Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).Circ Res, vol. 87, no. 8, Oct. 2000, pp. 705–09. Pubmed, doi:10.1161/01.res.87.8.705.
Kilts JD, Gerhardt MA, Richardson MD, Sreeram G, Mackensen GB, Grocott HP, White WD, Davis RD, Newman MF, Reves JG, Schwinn DA, Kwatra MM. Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i). Circ Res. 2000 Oct 13;87(8):705–709.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

October 13, 2000

Volume

87

Issue

8

Start / End Page

705 / 709

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Signal Transduction
  • Receptors, Serotonin
  • Receptors, Histamine
  • Receptors, Glucagon
  • Receptors, Cell Surface
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-1
  • Precipitin Tests
  • Photoaffinity Labels