| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1988: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Using primary culture of cardiocytes prepared from collagenase-dispersed atrial and ventricular myocytes of neonatal rats, we have studied the cellular mechanism of synthesis and secretion of atrial natriuretic peptide (ANP). Dexamethasone, testosterone, and thyroid hormone dose-dependently stimulated synthesis and secretion of ANP in cultured atrial myocytes. Cellular content of ANP in ventricular myocytes was far less than that in atrial myocytes. However, dexamethasone, testosterone, and thyroid hormone similarly stimulated synthesis and secretion of ANP, although ventricular myocytes were more responsive to dexamethasone than atrial myocytes. These data suggest that synthesis of ANP in cardiocytes is regulated by multihumoral factors including glucocorticoid, androgen, and thyroid hormone, and that tissue-dependent difference in glucocorticoid sensitivity exists between atrial and ventricular myocytes. -Adrenergic and muscarinic cholinergic agonists stimulated ANP secretion from atrial myocytes. Ca-ionophore and protein kinase C (PKC)-activating phorbol ester had stimulatory effect on ANP secretion, while coaddition of both compounds had synergistic effect. These data suggest that neural factor, especially -adrenergic and muscarinic cholinnergic receptors, is involved in ANP secretion, through a common signal transduction system involving phosphatidylinositol response, generating two second messengers, inositol triphosphate and diacylglycerol which mobilize intracellular Ca and activates PKC, respectively. Endothelin, a novel endothelium-derived vasoconstrictive peptide, had a potent stimulatory effect on ANP secretion from cultured atrial myocytes in a similar fashion as did voltage-dependent Ca-channel agonist, suggesting that endothelin may be an endogenous agonist of ANP secretion mainly via Ca influx.
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