Renal dopamine receptors: Characterization, autoradiographic localization, and functional studies.
Item
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Title
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Renal dopamine receptors: Characterization, autoradiographic localization, and functional studies.
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Identifier
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AAI9108120
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identifier
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9108120
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Creator
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Huo, Teh-Li.
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Contributor
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Adviser: Dennis P. Healy
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Date
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1990
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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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Health Sciences, Pharmacology | Health Sciences, Medicine and Surgery | Biology, Animal Physiology
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Abstract
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Dopamine, a precursor of norepinephrine and epinephrine, has its own specific receptors in the kidney. Dopamine has profound physiological effects in the kidney such as vasodilatation, natriuresis, and diuresis via activation of renal dopamine receptors. The mechanisms involved in the receptor-mediated events or post-receptor signaling of renal dopaminergic system, however, have not been resolved. The renal DA{dollar}\sb1{dollar} receptor has been reported to produce a renal vasodilatation and inhibition of sodium reabsorption in the proximal tubules by inhibition of Na{dollar}\sp{lcub}+{rcub}{dollar}/K{dollar}\sp{lcub}+{rcub}{dollar} ATPase and the Na{dollar}\sp{lcub}+{rcub}{dollar}/H{dollar}\sp{lcub}+{rcub}{dollar} antiporter. The role of the DA{dollar}\sb2{dollar} receptors in the actions of dopamine in the kidney was unclear.;The present study was to characterize and localize DA{dollar}\sb1{dollar} and DA{dollar}\sb2{dollar} receptors and to further determine the functions of the DA{dollar}\sb2{dollar} receptors in the rat kidney. The localization of the DA{dollar}\sb1{dollar} receptors was restricted to cortex, primarily in the proximal tubules. The results were compatible with a tubular site of action for dopamine in the kidney. The DA{dollar}\sb2{dollar} receptors were localized primarily in the inner medullary collecting ducts with a lower density in the cortex. Radioligand binding and photoaffinity labeling experiments indicated that the medullary dopamine receptor may be a novel DA{dollar}\sb2{dollar} receptor, because the renal DA{dollar}\sb2{dollar} receptor exhibited an unique competition pattern but with similar receptor molecular weight compared with the central D{dollar}\sb2{dollar} receptors. An endogenous dompaminergic system was found in the inner medullary collecting ducts (IMCD). IMCD cells have the capacity to synthesize dopamine from L-dopa locally via aromatic L-amino acid decarboxylase in the IMCD cells. Dopamine stimulated prostaglandin E{dollar}\sb2{dollar} (PGE{dollar}\sb2{dollar}) synthesis via activation of the DA{dollar}\sb2{dollar} receptors in cultured IMCD cells. The secondary messengers for dopamine-stimulated PGE{dollar}\sb2{dollar} were unknown but activation of phospholipase A{dollar}\sb2{dollar} and intracellular calcium were suggested. PGE{dollar}\sb2{dollar} is known to be a potent inhibitor of vasopressin action. Dopamine was also able to inhbit vasopressin-stimulated cyclic AMP accumulation via activation of the {dollar}\alpha\sb2{dollar}-adrenoceptors in IMCD cells. Therefore, it is possible to speculate that dopamine in the inner medulla can inhibit vasopressin-mediated hydro-osmotic effect via two mechanisms: (a) directly via {dollar}\alpha\sb2{dollar}-adrenoceptor inhibition of adenylate cyclase activity, and (b) indirectly via synthesis of PGE{dollar}\sb2{dollar}. The hypothesis is, therefore, that dopamine may be a functional antagonist of vasopressin in the renal medulla.
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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.
