The role of calcium, cyclic-AMP, osmotic forces and pH in controlling renin release from renal cortical slices and isolated renin-containing granules.
Item
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Title
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The role of calcium, cyclic-AMP, osmotic forces and pH in controlling renin release from renal cortical slices and isolated renin-containing granules.
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Identifier
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AAI8914791
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identifier
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8914791
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Creator
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Sigmon, David Henry.
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Contributor
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Adviser: John C. S. Fray
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Date
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1988
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, General | Biology, Animal Physiology
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Abstract
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These studies sought, in part, to elucidate the roles of calcium, cAMP, and chemiosmotic forces in the regulation of renin secretion. Renin was measured as renin activity. A 20-fold decrease in the rate of renin secretion was observed when cytosolic calcium concentrations was raised from 10{dollar}\sp{lcub}-8{rcub}{dollar}M to 10{dollar}\sp{lcub}-5{rcub}{dollar}M. These findings support the hypothesis that renin secretion is inversely related to cytosolic free-calcium. However, cAMP stimulated renin secretion by a fixed amount (250 ng Angiotensin I per 100 mg tissue per hr) when cytosolic calcium ranged from 10{dollar}\sp{lcub}-8{rcub}{dollar}M to 10{dollar}\sp{lcub}-5{rcub}{dollar}M. The dissociation between cytosolic calcium and cAMP suggests that there are two pathways governing the regulation of renin secretion, one calcium-dependent and the other calcium-independent.;Renal cortical slices and isolated granules were also used to investigate the roles of osmotic forces and pH gradients in the regulation of renin secretion and granular lysis. Renin secretion from renal cortical slices was inhibited by carbonyl-cyanide m-chlorophenylhydrazone (CCCP) and oligomycin. The effect of CCCP was pH-dependent, with maximal inhibition at alkaline pHs. Hypo-osmolality stimulated renin secretion in both cortical slices and isolated granules. The pH effect was biphasic with greater stimulation under strongly acid and alkaline conditions. In isolated granules, the pH effect was chloride and potassium dependent. Removal of either of these ions from the incubation medium inhibited granule release and lysis. 4-acetamido-4{dollar}\sp\prime{dollar}-isothiocyanatostilbene-2,2 disulfonic acid (SITS) and 4,4-diisothiocyanatostilbene-2,2{dollar}\sp\prime{dollar}- disulfonic acid (DIDS), two anion channel blockers, were without effect. The pH effect on isolated granule was abolished by addition of oligomycin and N,N{dollar}\sp\prime{dollar}-dicyclohexylcarbodiimide (DCCD) at pH 5 but not at pH 8; it was enhanced by NH{dollar}\sbsp{lcub}4{rcub}{lcub}+{rcub}{dollar}. Neither valinomycin nor CCCP was effective when presented alone, but in combination they stimulated at all pHs.;The data suggest that swelling of the renin granule, driven by a proton gradient across the granule membrane provides the driving force for renin secretion in a manner consistent with the chemiosmotic mechanism postulated for exocytotic release in other systems. These findings are discussed in terms of a chemiosmotic mechanism for exocytotic release of renin.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
