title: Phospholipase C signaling tonically represses basal atrial natriuretic factor secretion from the atria of the heart.
abstract: The cardiac hormone atrial natriuretic factor (ANF or ANP) plays significant, well-established roles in a large number of physiological and pathophysiological processes, including water and electrolyte balance, blood pressure regulation, and cardiovascular growth. Understanding the regulation of its production and secretion by atrial cardiomyocytes is incomplete. We have previously established a significant role of G(i/o) protein signaling in modulating ANF secretion as promoted by stretch of the atrial myocardium. In the present study, we investigated the role of G(q) protein signaling and its relationship to G(i/o) protein signaling using pharmacological manipulation of proximal effectors of G(αq) in an ex vivo model of spontaneously beating rat atria. Phospholipase C (PLC) and protein kinase C (PKC) inhibitors dramatically increased basal secretion of ANF. Furthermore, although atrial wall stretch is a potent stimulus for secretion, stretch unexpectedly reduced ANF secretion to basal levels under PLC and PKC inhibitory conditions. Inhibition of the inositol triphosphate receptor did not appear to affect basal secretion but dose-dependently blocked stretch-secretion coupling. The results obtained demonstrate that the PLC and PKC signaling cascades play important albeit unexpected roles in the regulation of basal and stimulated ANF secretion and suggest interplay between the G(q) and G(i/o) protein signaling pathways.
authors.affiliation: Department of Internal Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Astra I
authors.initials: AI
authors.lastname: Chang
authors.forename: Monica Forero
authors.initials: MF
authors.lastname: McGrath
authors.forename: Adolfo J
authors.initials: AJ
authors.lastname: de Bold
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D015544:Inositol 1,4,5-Trisphosphate; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D010738:Type C Phospholipases
keywords: G proteins; atrial natriuretic factor; endocrine heart; inositol triphosphate receptor; phospholipase C; protein kinase C