Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- 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 Date
- October 13, 2000
Published In
Volume / Issue
- 87 / 8
Start / End Page
- 705 - 709
PubMed ID
- 11029407
Electronic International Standard Serial Number (EISSN)
- 1524-4571
Digital Object Identifier (DOI)
- 10.1161/01.res.87.8.705
Language
- eng
Conference Location
- United States