Calcium, its role in isoproterenol-stimulated atrial natriuretic peptide secretion by superfused rat atria.
The beta-adrenergic agonist isoproterenol stimulates immunoreactive atrial natriuretic peptide (IR-ANP) secretion by superfused rat atria in vitro. beta-Adrenergic agonists alter the cellular handling of calcium, which culminates in a rise in the systolic calcium concentration. This is achieved by increasing calcium influx through voltage-dependent calcium channels and by increasing the storage pool of calcium in the sarcoplasmic reticulum (SR). We therefore asked the question whether isoproterenol-stimulated IR-ANP secretion was dependent on the protein kinase A-induced rise in systolic calcium or was due to a direct effect of protein kinase A activation. Isolated rat left atria paced at 3 Hz were superfused in vitro. IR-ANP secretion was determined by radioimmunoassay of timed collections of the superfusate. Superfusion with 0.1 microM isoproterenol or 0.5 mM dibutyryl cyclic AMP increased IR-ANP secretion twofold. Stimulated IR-ANP secretion was lowered to near baseline by lowering the buffer calcium concentration from 1.8 to 0.2 mM or by adding to the superfusate 10 microM nitrendipine (a calcium-channel blocker) or 1 microM ryanodine (an inhibitor of SR calcium release). Superfusion of nonbeating, electrically quiescent left atria with 0.1 microM isoproterenol failed to stimulate IR-ANP secretion. We conclude: 1) Isoproterenol-stimulated IR-ANP secretion is dependent on calcium influx through voltage-dependent calcium channels and on the release of calcium from the SR. 2) Enhanced calcium influx alone is not adequate to maintain isoproterenol-stimulated IR-ANP secretion. 3) The SR appears to be the primary source of calcium for isoproterenol-stimulated IR-ANP secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Schiebinger
R J
RJ
Department of Medicine, Wayne State University, Detroit, Michigan.
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D009568:Nitrendipine / Q000494:pharmacology; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology
D012433:Ryanodine; D003994:Bucladesine; D009320:Atrial Natriuretic Factor; D009568:Nitrendipine; D007545:Isoproterenol; D002118:Calcium