Participation of G proteins in natriuretic peptide hormone secretion from heart atria.
The involvement of G proteins in the mechanism underlying the increased atrial natriuretic factor (ANF) secretion observed after atrial muscle stretch (stretch-secretion coupling) was assessed using a combined pharmacological, immunocytochemical, and tissue fractionation approach. It was found that G(i/o) inhibition by pertussis toxin (PTX) abolished stretch-secretion coupling without affecting baseline secretion through a mechanism that is independent of G(q) signaling agonists. Mastoparan-7, a G(i/o) agonist, significantly increased ANF secretion even in the absence of muscle stretch through a PTX-sensitive mechanism. By confocal and electron immunocytochemistry, ANF and G(o) partially colocalized, whereas ultracentrifugation analysis suggested the presence of two populations of granules, one of which was partially associated with G(o), as demonstrated by Western blotting. PTX did not affect basal or endothelin-1-stimulated ANF secretion, in line with the view that endothelin-1 signals mainly through G(q). It is concluded there are at least two types of regulated secretory processes in atrial cardiocytes: one is acutely responsive to muscle stretch and is PTX sensitive, and the other is G(q)mediated and PTX insensitive and may be responsible for changes in secretion after chronic changes in the neuroendocrine environment.
Bensimon
Michael
M
Cardiovascular Endocrinology Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Chang
Astra I
AI
de Bold
Mercedes L Kuroski
ML
Ponce
Amalia
A
Carreras
Daniel
D
De Bold
Adolfo J
AJ
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006325:Heart Atria / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D016253:Microscopy, Immunoelectron; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D045265:Natriuretic Peptides / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014461:Ultracentrifugation
D019332:Endothelin-1; D036341:Intercellular Signaling Peptides and Proteins; C084070:Mas7 protein, synthetic; D045265:Natriuretic Peptides; D010455:Peptides; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins