Mechanism of hyperosmolality stimulation of ANP secretion: its dependency on calcium and sodium.
The calcium dependency of hyperosmolality stimulation of atrial natriuretic peptide (ANP) secretion was determined using isolated superfused nonbeating rat left atrium. Increasing osmolality by 65, 85, and 100 mosmol/kgH2O by superfusion with sucrose produced a peak rise in ANP secretion of 1.8-, 2.0-, and 2.7-fold. To determine whether calcium influx played a role in osmolality (osm)-stimulated ANP secretion, atria were superfused with 2 mM lanthanum, a calcium antagonist. Lanthanum inhibited by 85% the response to a 100 mosmol/kgH2O increase in osm. The voltage-dependent calcium channel blocker isradipine had no effect on osm-stimulated ANP secretion, suggesting that calcium influx via voltage-dependent calcium channels was not playing a significant role. Likewise, depleting sarcoplasmic reticulum calcium with 1 microM ryanodine did not block the response to osm, suggesting that calcium influx was not adequate to induce consequential release of calcium from the sarcoplasmic reticulum. To determine whether calcium influx was via Na(+)-Ca2+ exchange, we determined the sodium dependency of osm-stimulated ANP secretion. Replacement of sodium with lithium or choline blocked the secretory response to 100 mosmol/kgH2O. We conclude that osm-stimulated ANP secretion is calcium and sodium dependent. Calcium influx via Na(+)-Ca2+ exchange is highly implicated as the mechanism of cellular calcium entry.
Schiebinger
R J
RJ
Department of Medicine, Wayne State University, Detroit 48201.
Joseph
C M
CM
Li
Y
Y
Cragoe
E J
EJ
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006982:Hypertonic Solutions; D017275:Isradipine / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology*; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters; D013395:Sucrose / Q000494:pharmacology
D002352:Carrier Proteins; D006982:Hypertonic Solutions; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D012433:Ryanodine; D013395:Sucrose; D007811:Lanthanum; D009320:Atrial Natriuretic Factor; D012964:Sodium; D002118:Calcium; D017275:Isradipine