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      Regulation of blood pressure by dopamine receptors.

      1 , ,
      Nephron. Physiology
      S. Karger AG

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          Abstract

          Dopamine is an important regulator of blood pressure. Its actions on renal hemodynamics, epithelial transport and humoral agents such as aldosterone, catecholamines, endothelin, prolactin, pro-opiomelanocortin, renin and vasopressin place it in central homeostatic position for regulation of extracellular fluid volume and blood pressure. Dopamine also modulates fluid and sodium intake via actions in the central nervous system and gastrointestinal tract, and by regulation of cardiovascular centers that control the functions of the heart, arteries and veins. Abnormalities in dopamine production and receptor function accompany a high percentage of human essential hypertension and several forms of rodent genetic hypertension. Some dopamine receptor genes and their regulators are in loci linked to hypertension in humans and in rodents. Furthermore, single nucleotide polymorphisms (SNPs) of genes that regulate dopamine receptors, alone or via the interaction with SNPs of genes that regulate the renin-angiotensin system, are associated with human essential hypertension. Each of the five dopamine receptor subtypes (D1, D2, D3, D4 and D5) participates in the regulation of blood pressure by mechanisms specific for the subtype. Some receptors (D2 and D5) influence the central and/or peripheral nervous system; others influence epithelial transport and regulate the secretion and receptors of several humoral agents (e.g., the D1, D3 and D4 receptors interact with the renin-angiotensin system). Modifications of the usual actions of the receptor can produce blood pressure changes. In addition, abnormal functioning of these dopamine receptor subtypes impairs their antioxidant function.

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          Most cited references36

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          Human hypertension caused by mutations in WNK kinases.

          Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.
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            Molecular mechanisms of human hypertension.

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              Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct.

              The substantia nigra in Parkinson's disease (PD) is depleted of dopaminergic neurons and contains fibrillar Lewy bodies comprising primarily alpha-synuclein. We screened a library to identify drug-like molecules to probe the relation between neurodegeneration and alpha-synuclein fibrilization. All but one of 15 fibril inhibitors were catecholamines related to dopamine. The inhibitory activity of dopamine depended on its oxidative ligation to alpha-synuclein and was selective for the protofibril-to-fibril conversion, causing accumulation of the alpha-synuclein protofibril. Adduct formation provides an explanation for the dopaminergic selectivity of alpha-synuclein-associated neurotoxicity in PD and has implications for current and future PD therapeutic and diagnostic strategies.
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                Author and article information

                Journal
                Nephron Physiol
                Nephron. Physiology
                S. Karger AG
                1660-2137
                1660-2137
                2003
                : 95
                : 2
                Affiliations
                [1 ] Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, USA. pjose01@georgetown.edu
                Article
                73676
                10.1159/000073676
                14610323
                954a1bf9-cd24-4c4a-9478-c0379a1f387f
                History

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