Differential coupling of m-cholinoceptors to Gi/Go-proteins in failing human myocardium

• Verfasst von: Mittmann, Clemens [VerfasserIn]
• Verfasst von: Pinkepank, Gunnar [VerfasserIn]
• Verfasst von: Stamatelopoulou, Sophia [VerfasserIn]
• Verfasst von: Wieland, Thomas [VerfasserIn]
• Verfasst von: Nürnberg, Bernd [VerfasserIn]
• Verfasst von: Hirt, Stefan [VerfasserIn]
• Verfasst von: Eschenhagen, Thomas [VerfasserIn]
• Titel: Differential coupling of m-cholinoceptors to Gi/Go-proteins in failing human myocardium
• Verf.angabe: Clemens Mittmann, Gunnar Pinkepank, Sophia Stamatelopoulou, Thomas Wieland, Bernd Nürnberg, Stefan Hirt, Thomas Eschenhagen
• E-Jahr: 2003
• Jahr: 25 July 2003
• Umfang: 9 S.
• Fussnoten: Gesehen am 07.04.2022
• Titel Quelle: Enthalten in: Journal of molecular and cellular cardiology
• Ort Quelle: New York, NY [u.a.] : Elsevier, 1970
• Jahr Quelle: 2003
• Band/Heft Quelle: 35(2003), 10, Seite 1241-1249
• ISSN Quelle: 1095-8584
• DOI: doi:10.1016/s0022-2828(03)00235-9
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Acetylcholine
• Sach-SW: Adenosine Diphosphate
• Sach-SW: Adenosine Diphosphate Ribose
• Sach-SW: Adult
• Sach-SW: Carbachol
• Sach-SW: Cell Membrane
• Sach-SW: Dose-Response Relationship, Drug
• Sach-SW: Female
• Sach-SW: GTP-Binding Protein alpha Subunits, Gi-Go
• Sach-SW: Guanosine Triphosphate
• Sach-SW: Humans
• Sach-SW: Immunoblotting
• Sach-SW: Light
• Sach-SW: Male
• Sach-SW: Middle Aged
• Sach-SW: Myocardium
• Sach-SW: Pertussis Toxin
• Sach-SW: Precipitin Tests
• Sach-SW: Receptors, Muscarinic
• Sach-SW: RNA, Messenger
• Sach-SW: Time Factors
• Sach-SW: Tissue Distribution
• K10plus-PPN: 1798097230

Abstract

Muscarinic acetylcholine receptors (mAChRs) mediate their main cardiac effects via pertussis toxin-sensitive G-proteins. Physiological effects differ considerably between atrium and ventricle, and it is unknown to which extent these differences derive from selective receptor-G-protein coupling or further downstream events. We have characterized specific coupling between mAChRs and Gi/Go-protein isoforms in atrial and ventricular myocardium by agonist-dependent photoaffinity labeling with [(32)P]azidoanilido GTP (aaGTP) and immunoprecipitation in sarcolemmal membranes from terminally failing human hearts. The total amount of mAChRs, as determined by specific binding of [(3)H]QNB, was significantly higher in right-atrial (RA +/- SEM, 959 +/- 68 fmol/mg, n = 4) than in left-ventricular membranes (LV, 582 +/- 53 fmol/mg, n = 6). Standardized immunoblots revealed that Gialpha-2 was the predominant subtype in both regions. A 40-kDa splice variant of Goalpha (Goalpha-1 and/or Goalpha-3) was almost exclusively detectable in RA. Levels of Gialpha-3 and a 39-kDa splice variant of Goalpha (Goalpha-2) were also higher in RA. Basal aaGTP binding was higher in RA than in LV for all Gialpha/Goalpha subtypes. The carbachol (10 micromol/l)-induced increase in aaGTP binding was significantly higher in RA than in LV for Goalpha-1/3 (336 +/- 95% of LV, n = 4) and for Gialpha-3 (211 +/- 83%), lower for Gialpha-2 (42 +/- 5%), and was similar in both regions for Goalpha-2 (130 +/- 62%). The differential coupling of mAChRs in human RA and LV suggests that the initiation of different physiological responses to mAChR stimulation starts with signal sorting at the receptor-G-protein level.