Calcium influx in platelet activating factor-induced atrial natriuretic peptide release in rat cardiomyocytes.
Atrial natriuretic peptide (ANP) is released from the myocardium after the activation of protein kinase C and/or ischemia, events that are associated with an increase in platelet activating factor (PAF) production in this tissue. In this study we demonstrate that PAF, but not lyso-PAF, induces a concentration-dependent increase in ANP secretion in spontaneously beating neonatal rat cardiomyocytes, a response associated with increases in cellular adenosine 3',5'-cyclic monophosphate (cAMP) formation, calcium influx, and the mobilization of calcium from intracellular stores. cAMP formation and calcium influx appear to play major roles in PAF-induced ANP secretion in this system, insofar as PAF-induced ANP release was substantially reduced in the presence of the (R)-p-diastereoisomer of adenosine 3',5'-cyclic monophosphorothioate (10 microM), whereas both PAF-induced calcium influx and ANP secretion were abolished in the presence of the calcium channel antagonist nifedipine (0.1 microM). Consistent with these results, N6-2'-O-dibutyryl cAMP (DBcAMP, 10 microM) and/or forskolin (0.1 microM) simultaneously increased cAMP production, calcium influx, and ANP release in these cells, with both DBcAMP- and forskolin-induced ANP secretion being fully abolished in the presence of 0.1 microM nifedipine. Taken together, these results suggest that PAF, DBcAMP, and forskolin promote ANP secretion in spontaneously beating cardiomyocytes via the activation of a cAMP-dependent, nifedipine-sensitive myocardial calcium channel and that calcium influx is a major requirement for cAMP-induced ANP secretion in this system.
Church
D J
DJ
Department of Medicine, Geneva University Hospital, Geneva, Switzerland.
van der Bent
V
V
Vallotton
M B
MB
Capponi
A M
AM
Lang
U
U
D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats
C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D002118:Calcium