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)

Among other defects in water metabolism, adrenal insufficiency is associated with an inability to concentrate urine maximally in both man and experimental animals. Recent studies in the rabbit cortical collecting tubule have suggested indirectly that this defect may result from impaired cyclic AMP (cAMP) formation in response to antidiuretic hormone stimulation. In the present study, we examined key elements of arginine vasopressin (AVP)-dependent cAMP metabolism in the papillary collecting duct (PCD), microdissected from 8-d adrenalectomized (ADX) and sham-operated control rats. AVP-sensitive adenylate cyclase (ADC) activity in PCD did not differ between control and ADX rats. cAMP-phosphodiesterase activity (cAMP-PDIE), measured at 10(-6) M cAMP substrate concentration, was significantly higher (delta + 31.6%) in PCD of ADX rats compared with controls. Incubation of intact PCD from ADX rats with AVP resulted in an accumulation of cAMP (delta - 48.5%) significantly lower than observed in control PCD. Chronic administration of dexamethasone reduced cAMP-PDIE activity in PCD of ADX rats to levels close to or below those observed in control rat PCD, and also resulted in a restoration of AVP-stimulated cAMP accumulation to levels approaching control values. Results indicate that the impaired maximal urinary concentrating ability associated with adrenal insufficiency may be due, at least in part, to a reduced accumulation of cAMP in response to AVP in the PCD. This decreased cAMP accumulation results from increased cAMP-PDIE activity in the PCD of ADX rats and can be corrected by administration of glucocorticoid.
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PMID:Concentrating defect in the adrenalectomized rat. Abnormal vasopressin-sensitive cyclic adenosine monophosphate metabolism in the papillary collecting duct. 630 13

Because mammalian distal nephron segments with both calcitonin- and antidiuretic hormone- (ADH) sensitive adenylate cyclase activity have been described, in vivo and in vitro experiments were performed to study the effect of calcitonin on rat distal nephron water permeability. Calcitonin 1 and 0.1 U/ml, but not 0.01 U/ml, significantly increased the diffusional water permeability in the isolated papillary collecting duct by 15 and 11%, respectively. However, this effect was small when compared with a 68% increase with a supramaximal concentration of ADH (from 4.0 +/- 0.3 to 6.7 +/- 0.9 microns/s; n = 6, P less than 0.01). The normal increase in water permeability with increasing concentration of ADH (0.02 and 0.2 mU/ml) was depressed by the previous addition of calcitonin (1 U/ml) to the bath but was unaltered with the supramaximal ADH concentration (2 mU/ml). Verapamil, a compound that antagonizes cellular calcium entry, did not alter the effect of calcitonin on diffusional water permeability. Calcitonin in concentrations of 0.05, 0.5, and 5 U/ml produced a significant reduction in urine flow and free water clearance. Pretreatment with calcitonin in these concentrations inhibited the antidiuretic action of ADH. These studies suggest that calcitonin acts as a partial agonist to ADH within the distal nephron. It is unclear whether such an action represents a physiological or a pharmacological effect.
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PMID:Effect of calcitonin on urine concentration in the rat. 683 40

It is unclear whether the diuretic effects of atrial natriuretic peptide (ANP) result, in part, from an inhibition of the renal actions of vasopressin. Moreover, accruing evidence suggests that the kidneys themselves may produce an ANP-like peptide, urodilatin, which shares many of the renal actions of ANP. The mechanism underlying the diuretic action of urodilatin has not yet been examined. Accordingly, we have investigated the potential modulatory actions of both ANP and urodilatin on vasopressin-stimulated cyclic AMP (cAMP) production in microdissected inner medullary collecting duct (IMCD) segments of rat kidney. ANP and urodilatin alone (at 10(-8) or 10(-6) M) had no demonstrable effect on cAMP accumulation in IMCD segments. Moreover, neither ANP nor urodilatin (each at 10(-6) M) significantly altered either the profile or the absolute magnitude of the cAMP response stimulated by vasopressin. These findings indicate that neither ANP nor urodilatin interacts with the vasopressin-sensitive adenylate cyclase site in the rat IMCD to contribute to its diuretic actions.
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PMID:Lack of effect of atrial natriuretic peptide and urodilatin on vasopressin-stimulated cyclic AMP production in microdissected rat inner medullary collecting ducts. 806 Apr 79

The antidiuretic hormone arginine vasopressin (AVP) receptors are G protein-coupled and have been divided into at least three types: V1a (vascular/hepatic) and V1b (anterior pituitary) receptors, which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca2+; and V2 (kidney) receptor, which is coupled to adenylate cyclase. Recently V1a and V2 receptor cDNAs were cloned. These cDNAs encode proteins with seven putative transmembrane domains and a similar structure to rhodopsin and other G protein-coupled receptors. Micro-localization of mRNA coding for V1a and V2 receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction. Large signals for V1a receptor PCR product were detected in glomerulus, cortical collecting duct (CCD), outer medullary collecting duct (OMCD), inner medullary collecting duct (IMCD), and arcuate artery. Large signals for V2 receptor PCR product were detected in CCD, OMCD, and IMCD. 72-hour dehydration caused decrease of V2 receptor mRNA, but no change in V1a receptor mRNA in rat IMCD. These data show that mRNA coding for the two AVP receptor subtypes are distributed differently along the nephron and renal vascular system, and that these mRNAs are regulated differently in response to the dehydrated state. Recently, two reports of a mutation in the vasopressin V2 receptor gene in a kindred with X-rinked nephrogenic diabetes insipidus are published. These studies demonstrated that point mutation of V2 receptor gene causes the nephrogenic diabetes insipidus. Understanding the nature of defective diabetes insipidus may ultimately lead to improved therapy.
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PMID:[Recent advances in vasopressin receptors and signal transduction system]. 825 35

Cisplatin is an antineoplastic agent. Several nephrotoxic effects are associated with its use including chronic and acute renal failure, renal magnesium wasting, and polyuria. We have investigated polyuria in groups of rats treated with cisplatin at doses of 2.5 and 5 mg/kg body weight given once weekly for 3 weeks to determine possible mechanisms of this impairment. After cisplatin administration, glomerular filtration rate was reduced and significant increases in sodium and water loss were also seen. These changes were associated with decreases in urinary cAMP. Inner medullary collecting duct (IMCD) cells were removed from these animals and were stimulated with graded doses of vasopressin. Cells from cisplatin-treated rats showed an impaired response in cAMP generation to vasopressin stimulation as compared to cells from normal animals. To determine more precisely the site of impairment, the adenylate cyclase complex of the IMCD cells was further studied with forskolin and NaF. Forskolin was used to probe the catalytic unit activating adenylate cyclase, and NaF the guanine nucleotide regulatory protein (G protein). In response to forskolin, cells from cisplatin-treated rats and normal rats responded similarly in generating cAMP. However, following NaF, the cAMP response was blunted in the cells from the cisplatin rats. These results suggested that the catalytic unit was not injured by cisplatin (forskolin study) but the G protein was (NaF). In conclusion, the present study suggests that the polyuria seen following cisplatin administration is associated with an end-organ resistance to vasopressin manifested by reduced cAMP generation, secondary in part or whole to a defect at the level of the G protein.
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PMID:Mechanism of polyuria after cisplatin therapy. 830 21

In the rat cortical collecting duct (CCD), the presence of highly specific receptors to calcitonin (CT) coupled to a sensitive adenylate cyclase system suggests that this segment is a target site for CT. Our aim was to explore the effects of CT on the rat CCD microperfused in vitro. The hormone failed to alter the osmotic water permeability and did not affect net Na+ transport but generated a lumen-positive transepithelial potential difference (PDte), which under control conditions was close to zero. This response was dose dependent and was still observed in the presence of luminal amiloride, despite the luminal positivity generated by the Na+ channel blocker (PDte increased from 4.0 +/- 0.8 to 9.5 +/- 1.1 mV). In contrast, the nominal absence of CO2/HCO3- or the use of a low-Cl- solution totally prevented the PDte changes caused by CT. The CT-induced lumen-positive PDte was reduced by 2.3 +/- 0.8 mV after the basolateral addition of the Cl- channel inhibitor diphenylamine-2-carboxylate. 4-Acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid and acetazolamide, which inhibit Cl-/HCO3- exchangers and carbonic anhydrase activities, respectively, also inhibited the CT-induced PDte by 4.6 +/- 0.5 and 5.0 +/- 0.9 mV. To test whether the acid-base status of the animals influences the response to CT, rats underwent an acid or alkali load. CCD dissected from acid-loaded rats responded to CT to the same extent as control animals, but the hormonal action was significantly attenuated when the CCD was harvested from alkali-loaded rats (PDte increases: acid 4.0 +/- 0.3 vs. alkali 1.6 +/- 0.6 mV, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of calcitonin on function of intercalated cells of rat cortical collecting duct. 844 35

In vitro studies on single microdissected segments have been extensively used during the 20 past years to localize V1 and V2 vasopressin receptors within the mammalian kidney, and define their role in the control of water balance. Based on vasopressin-dependent adenylate cyclase activity measurements and quantitative RT-PCR studies, it is now clear that V2 receptors are present along the whole collecting duct from cortex to papilla, and, in most species, in the ascending limb of Henle's loop (thick and thin limb); occasionally in the distal tubule but not in the other segments. The stimulation by cyclic AMP of sodium chloride reabsorption in the thick ascending limb, and of urea reabsorption in the papillary collecting duct indicates that vasopressin--in addition to its well known hydroosmotic effect--also participates in the building up of the corticopapillary gradient of osmotic pressure. As regards the V1a receptor, binding studies as well as quantitative RT-PCR, and measurements of free cytosolic calcium concentration allow us to draw the following conclusions. In the rat, the V1a receptor is absent from the glomerulus, the proximal tubule (convoluted and straight portions), the tick ascending limb of Henle's loop and the terminal portion of the papillary collecting duct. It is present in the thin ascending limb and the cortical and outer medullary portions of the collecting duct. Its presence in the thin descending limb has not, up to now, been explored. By contrast with previous data in the rabbit, the V1a receptor does not alter vasopressin-dependent sodium and water reabsorption in the rat cortical collecting duct. Further studies will be necessary to determine its functional role in that segment, as well as in the thin ascending limb. Finally, vasopressin V2 agonists have been shown to induce intracellular calcium release in the papillary collecting duct, a segment devoid of V1a receptors. This effect--which cannot be ascribed to a cross-reaction with oxytocic receptors--indicates either an unusual coupling of the V2 receptor to phospholipase C or, else, the presence of a new vasopressin receptor.
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PMID:[Functional expression of vasopressin receptors V1a and V2 along the mammalian nephron]. 859 Feb 15

The present paper reviews the recent progress of analysis of nephrogenic diabetes insipidus (NDI). NDI has been considered as a X-linked recessive inheritance. Arginine vasopressin (AVP) V2 receptors were cloned and characterized its structural and functional properties. The gene of AVP V2 receptors is localized in X chromosome q27-28. The mutations of AVP V2 receptor gene have been clarified in patients with NDI. They accounted for approximately 30 kinds of mutations, including deletion and insertion of nucleotide, and point mutation of nucleotides. The mutant receptors have an inability to bind to AVP ligand or activate adenylate cyclase, a post-receptor signal transduction. Also, there are patients with NDI, who were considered as an autosomal dominant or autosomal recessive inheritance. Water channel aquaporin of collecting duct (AQP-2) was cloned and characterized, which is localized in chromosome 12q13. Recent studies elucidated the mutations of AQP-2 gene in several families with autosomal recessive NDI. Also, the mutations of AQP-2 gene were found in patients with NDI, who were thought as autosomal dominant inheritance. Therefore, both mutations of AVP V2 receptors and AQP-2 are involved in pathogenesis of NDI.
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PMID:[Nephrogenic diabetes insipidus]. 890 43

mIMCD-k2 cells are derived from the inner medullary collecting duct of a mouse and exhibit electrogenic sodium absorption and cAMP- and vasopressin (AVP)-stimulated electrogenic chloride secretion [N. L. Kizer, B. Lewis, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995; and N. L. Kizer, D. Vandorpe, B. Lewis, B. Bunting, J. Russell, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F854-F861, 1995]. The purpose of the present study was to determine how peptide YY (PYY) affects electrogenic Na+ and Cl- current in mIMCD-k2 cells. Short-circuit currents (Isc) were measured across monolayers of mIMCD-k2 cells mounted in Ussing-type chambers. PYY did not alter baseline Isc, nor did it alter Isc in chloride-free conditions, indicating no effect on electrogenic sodium transport. Baseline chloride current in these cells is low; therefore, chloride short-circuit current (IClsc) was stimulated with AVP (10 nM) added to the basolateral surface and 10 microM amiloride added to the apical surface. Although apical applications of PYY had no effect, basolateral application of PYY caused attenuation of IClsc, with the maximal inhibitory dose (100 nM) causing 52 +/- 1.3% inhibition (IC50 = 0.11 nM). Inhibition by PYY of IClsc is mediated through the Y2 receptor subtype, as PYY-(3-36) was the only PYY analog tested that caused inhibition and was equipotent to PYY. Inhibition by PYY of IClsc was abolished following incubation with pertussis toxin. We also show that PYY inhibits AVP-stimulated cAMP accumulation, with a maximal inhibitory dose (100 nM) causing a 38% +/- 6% inhibition (IC50 = 0.16 nM), comparable to inhibition by PYY of IClsc. We conclude that PYY acts through either Gi or Go to inhibit adenylate cyclase activity, leading to a decrease in AVP-stimulated chloride current.
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PMID:Peptide YY inhibits vasopressin-stimulated chloride secretion in inner medullary collecting duct cells. 972 20

The two neurohypophysial hormones arginine vasopressin (AVP) and oxytocin have actions in the inner medullary collecting duct (IMCD) where both peptides induce an increase in cAMP accumulation. The present study has employed a novel IMCD cell line to determine whether these two hormones induce cAMP accumulation via common or separate receptors, and to characterize the potential receptors responsible. Equal volumes of vehicle (150 mM NaCl) or hormone/antagonist solutions were added to aliquots of 10(4) IMCD cells in the presence of 10(-3) M 3-isobutylmethylxanthine (IBMX) and incubated at 37 degrees C for 4 min. cAMP levels were determined by radioimmunoassay and protein concentration by Bradford assay. Both AVP and oxytocin elicited dose-dependent increases in cAMP generation, though oxytocin was less potent than AVP (EC50 = 1.6 x 10(-8) M vs. 7.4 x 10(-10) M). AVP at 10(-8) M and oxytocin at 10(-8) M, concentrations sufficient to elicit near-maximal cAMP accumulation, resulted in cAMP levels of 73.4 +/- 1.7 and 69.0 +/- 3.3 pmol (mg protein)-1 (4 min)-1, respectively (n = 10), compared with the vehicle-treated basal value of 37.7 +/- 2.2 pmol (mg protein)-1 (4 min)-1 (P < 0.001, n = 10). Combined AVP (10(-8) M) and oxytocin 10(-6) M) resulted in cAMP accumulation of 63.8 +/- 3.1 pmol (mg protein)-1 (4 min)-1 (n = 10), which was not significantly different from the effect of oxytocin alone, but slightly less than that for AVP alone (P < 0.05). A submaximal concentration of AVP (10(-10) M) induced cAMP accumulation of 48.6 +/- 2.5 pmol (mg protein)-1 (4 min)-1 (P < 0.01 compared with basal level of 34.9 +/- 2.4 pmol (mg protein)-1 (4 min)-1, n = 10), which was blocked in the presence of a vasopressin V2 receptor antagonist (10(-7) M OPC-31260) but not by the oxytocin receptor antagonist (10(-6) M [Pen1,pMePhe2, Thr4,Orn8]oxytocin) (36.3 +/- 6.1 and 45.1 +/- 1.3 pmol (mg protein)-1 (4 min)-1 respectively, P < 0.05, n = 10). A submaximal concentration of oxytocin (10(-7) M) induced a cAMP accumulation of 45.8 +/- 1.8 pmol (mg protein)-1 (4 min)-1 (n = 10), which was reduced by addition of 10(-6) M oxytocin antagonist (36.3 +/- 2.1 pmol (mg protein)-1 (4 min)-1, P < 0.05, n = 10), whereas co-incubation with 10(-6) M of the V2 receptor antagonist had no effect (43.2 +/- 1.3 pmol (mg protein)-1 (4 min)-1, n = 10). These results indicate that AVP and oxytocin induce cAMP accumulation from a common ATP pool in IMCD cells, and that separate vasopressin V2 and oxytocin receptor systems are involved, perhaps coupled to a common adenylate cyclase system.
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PMID:Separate receptors mediate oxytocin and vasopressin stimulation of cAMP in rat inner medullary collecting duct cells. 1008 3


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