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

alpha 2-Adrenoceptor subtype expression was investigated in cultured rat inner medullary collecting duct (IMCD) cells using radioligand binding studies, Northern blot analysis, and adenosine 3',5'-cyclic monophosphate (cAMP) assays. [3H]rauwolscine bound to a single class of alpha 2-adrenoceptors with high affinity [Kd = 1.7 +/- 0.3 nM, maximum binding (Bmax) = 45.2 +/- 10.8 fmol/mg protein]. alpha 2-Adrenoceptor ligands inhibited [3H]rauwolscine binding with a rank order of potency characteristic of interaction with the alpha 2B-adrenoceptor [inhibitory constant (Ki) values (in nM) rauwolscine (1.95) greater than ARC-239 (8.52) greater than prazosin (237) greater than oxymetazoline (30,000)]. Northern blot analysis was performed using poly(A)+ RNA isolated from 90% confluent rat IMCD cells and probes derived from alpha 2-adrenoceptor DNA sequences from the rat nonglycosylated alpha 2B-adrenoceptor and the human alpha 2A-adrenoceptor. The alpha 2B probe hybridized to a 4.2-kb band under high stringency conditions, but the alpha 2A-adrenoceptor probe did not hybridize to this band. In functional studies, the full alpha 2-adrenoceptor agonists epinephrine and UK-14,304 potently inhibited vasopressin-stimulated cAMP accumulation by 50 to 70% [half-maximal response (EC50) (in nM) epinephrine = 11.2, UK-14,304 = 6.4]. Guanabenz and clonidine were partial agonists, inhibiting cAMP accumulation by 30 to 40% and were less potent than the full agonists [EC50 (in nM) 56.0 guanabenz and 94.5 clonidine]. Epinephrine-induced inhibition of cAMP accumulation was blocked by rauwolscine, prazosin, and ARC-239 but not by the alpha 1-adrenoceptor antagonist corynanthine. We conclude that rat IMCD cells in primary culture express functional alpha 2-adrenoceptors of the alpha 2B-subtype.
 ...
PMID:Characterization of prazosin-sensitive alpha 2 B-adrenoceptors expressed by cultured rat IMCD cells. 171 24

Guanabenz, a centrally acting alpha 2-agonist, has been shown to lower blood pressure (BP) while maintaining glomerular filtration rate and increasing water and solute excretion. The site and mechanism of the increased solute excretion are still unclear. To evaluate the effect of guanabenz on water and solute reabsorption in the collecting duct, Munich Wistar rats were utilized in micropuncture experiments. Micropuncture samples were obtained from the most proximal portion (base) of the collecting duct and the most distal part (tip). In an initial group of hydropenic rats, collecting duct water and chloride (Cl) reabsorption were evaluated during a control and experimental period during which guanabenz was infused at 20-40 micrograms/kg/min. Although the mean drop in BP was 18 mm Hg after guanabenz infusion, at any given rate of Cl delivery, the reabsorption was less than that for the control period. Another group of studies utilizing the plasma repletion method to increase Cl excretion was used to evaluate collecting duct reabsorption. BP was lowered in rats by an aortic snare to approximately 95 mm Hg and papillary collecting duct (PCD) samples were obtained. The snare was then released and 100-400 micrograms/kg/min of guanabenz was infused and the rate adjusted to produce a drop in BP similar to that of the initial period. During the control period, PCD fluid to plasma inulin ratios were 23.1 +/- 4.3 and 37.3 +/- 4.6 at the base and tip, respectively. This ratio was decreased to 10.9 +/- 3.1 and 15.7 +/- 4.6 at the base and tip puncture sites, respectively, during guanabenz infusion. PCD chloride reabsorption during the initial period was 40.3% +/- 7.0% of the load delivered. During the guanabenz infusion, however, only 12.8% +/- 3.4% of the delivered load was reabsorbed (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Delineation of the site of action of guanabenz in the renal tubule. 608 26