Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Norepinephrine stimulates renal tubular sodium reabsorption, probably through an alpha 1-adrenoceptor-mediated mechanism. Although the distribution of alpha 1-adrenoceptors in the kidney has been studied with autoradiography, the precise location of these receptors in isolated nephron segments is unclear. Using a microassay we determined the specific binding of [125I]iodoarylazidoprazosin ([125I]prazosin), a high specific radioactivity analog of the selective alpha 1-antagonist prazosin, to microdissected glomeruli and tubule segments. Specific binding of [125I]prazosin (3 nM) in the proximal convoluted tubule was time- and concentration-dependent, saturable, and reversible. In this segment the apparent KD by association and dissociation rate constants of [125I]prazosin binding was 0.47 nM, and the maximum receptor density was approximately 0.19 fmol/mm, or 720 fmol/mg protein. Binding specificity was verified in competition studies with excess (3 microM) unlabeled prazosin and probes for alpha 2- (yohimbine), beta- (propranolol), dopamine1- (SCH23390), and dopamine2- (S-sulpiride) receptors. [125I]Prazosin binding was inhibited significantly only by unlabeled prazosin. Mapping of prazosin binding along the nephron revealed that the highest density was in the proximal convoluted tubule, followed by the proximal straight tubule. Lesser binding was found in the thick ascending limb and in the distal convoluted tubule, whereas in the cortical and outer medullary collecting duct and in glomeruli, binding was not significantly different from zero.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal adrenergic receptors: localization of [125I]prazosin binding sites along the microdissected rat nephron. 145 Oct 23

Recent work has demonstrated that alpha 1-adrenergic receptors are composed of at least two subtypes, termed alpha 1a and alpha 1b. It has been proposed that these subtypes may be linked to distinct second messenger systems. In the current studies, we have compared the properties of alpha 1-adrenergic receptors in rat renal cortical membranes with those in MDCK-D1 cells, a clonal cell line derived from distal tubule/collecting duct. Competitive binding studies with [3H]prazosin and compounds [5-methylurapidil, (+)-niguldipine, WB4101, and oxymetazoline] that distinguish high affinity (alpha 1a) and low affinity (alpha 1b) sites indicated that rat renal cortical membranes contain about 50% of each class of site. In contrast, MDCK-D1 cells contained a single population of low affinity sites. 5-Methylurapidil, but not the other compounds, recognized binding sites in these cells with a substantially lower affinity than has been observed for the low affinity site in other tissues and in parallel studies with renal cortical membranes. [3H]Prazosin binding sites in these cells, as well as alpha 1-adrenergic receptor-mediated arachidonic acid release and phosphoinositide and phosphatidylcholine hydrolysis, were sensitive to inactivation by chloroethylclonidine (IC50 approximately 0.7 microM), as expected for alpha 1b receptors. However, alpha 1-adrenergic receptors of MDCK-D1 cells required extracellular calcium for biological response, unlike what has been hypothesized for the alpha 1b receptor subtype. These data indicate that the population of alpha 1-adrenergic receptors of distal tubule/collecting duct cells likely consists of receptors of the alpha 1b subtype. The low affinity binding of 5-methylurapidil and the requirement for extracellular calcium for biological response in these cells suggest that this receptor may not be identical to the alpha 1b receptor that has been observed in other systems.
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PMID:Renal alpha 1-adrenergic receptor subtypes: MDCK-D1 cells, but not rat cortical membranes possess a single population of receptors. 184 62

Arginine vasopressin (AVP) increases water permeability in the collecting duct of the nephron via activation of adenylyl cyclase. Alpha-2 (alpha2) agonists inhibit AVP-stimulated water permeability via binding to alpha2 adrenoceptors that have been divided into 3 subtypes- alpha2A, alpha2B, and alpha2C. Some biological effects mediated by alpha2 agonists result from nonadrenergic imidazoline receptors that exist in the rat kidney. Thus, alpha2-inhibition of AVP-stimulated water permeability in the rat collecting duct could be caused by imidazoline receptors. The purpose of this study was to test agonists and antagonists selective for alpha2 and imidazoline receptors on AVP-stimulated water permeability in the rat inner medullary collecting duct (IMCD). Some experiments were conducted where water permeability was stimulated by a nonhydrolyzable analog of adenosine 3', 5'-cyclic monophosphate (cAMP). Agonists included dexmedetomidine, clonidine, oxymetazoline, agmatine and rilmenidine. The latter two are selective imidazoline agonists. Antagonists included yohimbine, RX821002, atipamezole, prazosin, WB4101, idazoxan, and BU239. Prazosin and WB4101 demonstrate selectivity for the alpha2B and alpha2C subtypes, respectively, and oxymetazoline and RX821002 are selective for the alpha2A subtype. BU239 is selective for imidazoline receptors. Wistar rat terminal IMCDs were isolated and perfused to determine the osmotic water permeability coefficient (Pf). All agonists except agmatine inhibited AVP-stimulated Pf. Inhibition by rilmenidine indicated a different mechanism of action from other agonists. Dose-response data show dexmedetomidine to be the most potent inhibitor. Oxymetazoline and clonidine inhibited cAMP-stimulated Pf indicating that the mechanism involves postcAMP cellular events. It was reported previously that dexmedetomidine inhibits cAMP-stimulated Pf (1). All antagonists except prazosin and WB4101 reversed alpha2-inhibition of AVP-stimulated Pf. BU239 was effective at 1 microM but not at 100 nM. Results suggest that alpha2A adrenoceptors modulate water permeability in the IMCD. The involvement of imidazoline receptors is inconclusive.
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PMID:Inhibition of water permeability in the rat collecting duct: effect of imidazoline and alpha-2 compounds. 1035 25