Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P41181 (collecting duct)
5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied cyclic 3',5'-nucleotide phosphodiesterase (PDE) isozymes and their role in adenosine 3',5'-cyclic monophosphate (cAMP) and cGMP metabolism in a rat inner medullary collecting duct (IMCD) cell line. The homogenized and fractionated IMCD cells of cAMP-PDE and all of cGMP-PDE activity were found in the cytosol. The majority of cytosolic cAMP-PDE (greater than 50%) was isozyme PDE-IV; the Ca(2+)-calmodulin-sensitive PDE-I was present only in cytosol. Preincubation of IMCD cells with PDE-IV inhibitor rolipram markedly (5x) enhanced levels of cAMP both basal and in the presence of [Arg8]vasopressin (AVP). Cilostamide (for PDE-III) or vinpocetine had no effect, whereas PDE-I inhibitor 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MeoM-IBMX) enhanced AVP-dependent cAMP levels. Exposure of IMCD cells to 2 microM ionomycin decreased both basal and AVP-stimulated cAMP. Depletion of Ca2+ by preincubation of IMCD cells in the Ca(2+)-free medium with ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid markedly enhanced the stimulatory response of cAMP to AVP, and addition of 8-MeoM-IBMX further enhanced the AVP response. The levels of cGMP, basal or in response to atriopeptin (ANP), were not affected by PDE-V inhibitor zaprinast, but both inhibitors of PDE-I, 8-MeoM-IBMX and vinpocetine, increased basal cGMP, and 8-MeoM-IBMX also increased cGMP levels enhanced by ANP. The depletion of Ca2+ from IMCD cells alone had no effect on cGMP levels, but effects of 8-MeoM-IBMX and vinpocetine on the ANP-stimulated cGMP levels were enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Cyclic 3',5'-nucleotide diesterases in dynamics of cAMP and cGMP in rat collecting duct cells. 132 Mar 33

Experimental nephrotic syndrome results in sodium retention, reflecting, at least in part, an intrinsic defect in renal sodium handling in the distal nephron. We studied the relationships among plasma atrial natriuretic peptide (ANP) concentration, sodium excretion (UNaV), and urinary cyclic GMP excretion (UcGMPV) in vivo, and the responsiveness of isolated glomeruli and inner medullary collecting duct (IMCD) cells to ANP in vitro, in rats with adriamycin nephrosis (6-7 mg/kg body weight, intravenously). 3-5 wk after injection, rats were proteinuric and had a blunted natriuretic response to intravenous infusion of isotonic saline, 2% body weight given over 5 min. 30 min after onset of the infusion, plasma ANP concentrations were elevated in normals and were even higher in nephrotics. Despite this, nephrotic animals had a reduced rate of UcGMPV after the saline infusion, and accumulation of cGMP by isolated glomeruli and IMCD cells from nephrotic rats after incubation with ANP was significantly reduced compared to normals. This difference was not related to differences in binding of 125I-ANP to IMCD cells, but was abolished when cGMP accumulation was measured in the presence of 10(-3) M isobutylmethylxanthine or zaprinast (M&B 22,948), two different inhibitors of cyclic nucleotide phosphodiesterases (PDEs). Infusion of zaprinast (10 micrograms/min) into one renal artery of nephrotic rats normalized both the natriuretic response to volume expansion and the increase in UcGMPV from the infused, but not the contralateral, kidney. These results show that, in adriamycin nephrosis, blunted volume expansion natriuresis is associated with renal resistance to ANP, demonstrated both in vivo and in target tissues in vitro. The resistance does not appear related to a defect in binding of the peptide, but is blocked by PDE inhibitors, suggesting that enhanced cGMP-PDE activity may account for resistance to the natriuretic actions of ANP observed in vivo. This defect may represent the intrinsic sodium transport abnormality linked to sodium retention in nephrotic syndrome.
...
PMID:Cellular basis for blunted volume expansion natriuresis in experimental nephrotic syndrome. 132 96

Dopamine decreases tubular sodium reabsorption, attributed in part to Na/K-ATPase inhibition in the proximal convoluted tubule (PCT). Because the final regulation of sodium excretion occurs in the collecting duct, where we have demonstrated specific dopamine DA1 binding sites, we examined the effects of dopamine, and of DA1 and DA2 receptor agonists on the Na/K pump in the microdissected rat cortical collecting duct (CCD) and in Madin-Darby canine kidney (MDCK) cells, a line derived from the dog distal nephron. Dopamine inhibited pump activity in CCD by approximately 40%-50%, an effect proportionally larger than in the PCT. Unlike in the latter, the effect of dopamine was reproduced by the DA1 agonist fenoldopam, which inhibited the CCD pump in dose-dependent manner (maximum, 10 microM). The DA2 agonist quinpirole was without effect, either alone or in combination with fenoldopam. These actions on Na/K-ATPase paralleled in reciprocal fashion effects on adenylate cyclase: dopamine or fenoldopam, but not quinpirole, produced a significant increase in cAMP content, and the stimulation by dopamine was blocked by SCH 23390. Inhibitors of cAMP phosphodiesterase (3-isobutyl-1-methyl-xanthine and theophylline), as well as forskolin and dibutyryl-cAMP, mimicked the effect of dopamine on the pump, underscoring the role of increased cAMP in this phenomenon. Both dopamine and fenoldopam inhibited Na/K-ATPase activity in MDCK cells. The results indicate that besides the PCT dopamine inhibits Na/K-ATPase activity in cells of the distal nephron, where its effect on the pump appears to be more pronounced and is mediated by activation of the DA1 receptor. The natriuretic effect of dopamine is probably exerted at both proximal and distal nephron sites.
...
PMID:Dopamine inhibits Na/K-ATPase in single tubules and cultured cells from distal nephron. 135 25

We investigated the tubular action of endothelin in rat nephron segments. The effects of endothelin on arginine vasopressin (AVP)-, parathyroid hormone-, glucagon-, calcitonin-, and isoproterenol-dependent cAMP accumulation were studied. The following nephron segments were microdissected: glomerulus (Gl), proximal convoluted tubule (PCT), cortical and medullary thick ascending limbs of Henle's loop (cTAL and mTAL, respectively), cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and inner medullary collecting duct (IMCD). Endothelin dose dependently (10(-8)-10(-10)M) inhibited AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD. This effect was independent of the presence or absence of phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, Ca channel blocker nicardipine, or indomethacin, but was abolished in the presence of protein kinase C inhibitor H-7. Protein kinase C stimulator dioctanoyl glycerol mimicked the effect of endothelin. On the other hand, endothelin had no inhibitory effect on AVP-dependent cAMP accumulation in cTAL or mTAL, parathyroid hormone-dependent cAMP accumulation in Gl and PCT, or glucagon-, calcitonin-, and isoprotereol-dependent cAMP accumulation in OMCD. We conclude that endothelin specifically inhibits AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD through activating protein kinase C. This effect possibly has a role in maintaining urine volume to counteract the decrease in GFR caused by endothelin itself.
...
PMID:Effects of endothelin on peptide-dependent cyclic adenosine monophosphate accumulation along the nephron segments of the rat. 169 79

Administration of adenosine (Ado) into rat renal artery induces dose-dependent diuresis that is independent of changes in glomerular filtration rate or renal blood flow, suggesting a direct effect on tubule H2O reabsorption. To test the hypothesis that Ado modulates cellular action of arginine vasopressin (AVP) as a tubular mechanism for the diuretic effect of Ado, interaction of Ado with AVP was studied in primary cell culture of rat inner medullary collecting duct (IMCD) epithelium. Stimulation of cells with 10(-6) M AVP in presence of 0.1 mM Ro 20-1724, a nonmethylxanthine phosphodiesterase inhibitor that has no effect on Ado receptors, increased adenosine 3',5'-cyclic monophosphate (cAMP) levels twofold or more above baseline. Stimulation of cells with the A1 Ado-receptor agonist N6-cyclohexyladenosine (CHA), the A2-receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA), or with the P-site agonist 2',5'-dideoxyadenosine (DDA) significantly inhibited the AVP-stimulated cAMP response. Preincubation with pertussis toxin abolished the inhibitory effects of CHA and NECA, but not of DDA. The data suggest that, in the rat IMCD, Ado modulates AVP action by interfering with its ability to stimulate formation of its second messenger, cAMP. This effect is mediated by the extracellular Ado receptors A1 and A2 and by the intracellular P-site. It occurs by at least two pathways, one sensitive and the other insensitive to pertussis toxin.
...
PMID:Interaction of adenosine with vasopressin in the inner medullary collecting duct. 217 61

Atrial natriuretic peptides (ANP) stimulate renal Na+ excretion by poorly understood mechanisms, possibly involving direct inhibition of Na+ transport in the renal medulla. We have previously shown that human ANP 4-28 (hANP) inhibits Na+ entry-dependent O2 consumption (QO2) in rabbit inner medullary collecting duct (IMCD) cells. Because ANP actions in other tissues appear to be mediated by guanosine 3',5'-cyclic monophosphate (cGMP), the present studies examined the role of cyclic nucleotides in IMCD cell responses to ANP. 8-Bromo-cGMP (8-BrcGMP) diminished QO2 by 23.5 +/- 1.2% (SE) in IMCD cells but had no effect in cells derived from outer medullary collecting duct (OMCD); dibutyryl-adenosine 3',5'-cyclic monophosphate (cAMP) was without effect in IMCD cells. The inhibitory effect of BrcGMP was not additive with ANP, amiloride, or ouabain. Amphotericin, which enhances Na+ entry into cells, prevented the inhibitory effect of 8-BrcGMP. These results indicate that 8-BrcGMP, like ANP, inhibited Na+ entry in IMCD cells. hANP stimulated a 10-fold increase in cGMP in IMCD cells without altering IMCD cAMP levels or OMCD cGMP levels. Isobutyl methylxanthine, which inhibits phosphodiesterase activity, enhanced both cGMP accumulation and inhibition of QO2 by submaximal levels (10(-9) M) of ANP. Nitroprusside raised cGMP levels in both IMCD and OMCD cells but inhibited QO2 only in IMCD cells. We conclude that cGMP mediates the transport effects of ANP in IMCD cells. Our results indicate that cGMP may play an important role in the regulation of sodium transport in renal epithelia.
...
PMID:cGMP mediates effects of atrial peptides on medullary collecting duct cells. 243 76

We have demonstrated previously that atrial natriuretic factor (ANF) augments urinary, plasma and kidney cGMP levels but has no significant effect upon cAMP. Using cGMP as a marker, we searched for specific target sites involved in the action of ANF in the dog kidney, and observed no change of cGMP in the proximal tubules, a 2-fold increase over basal levels in the thick loop of Henle and a 3-fold elevation in the collecting duct. The most striking action on cGMP occurred in the glomeruli with a rise of up to 50-fold being evident at 1-2 min. after the addition of ANF. The results obtained in the absence or presence of a phosphodiesterase inhibitor support the notion that the effects of ANF were exerted at the level of guanylate cyclase stimulation rather than cGMP phosphodiesterase inhibition. The action of sodium nitroprusside (SNP), a direct stimulator of soluble guanylate cyclase, differed from that of ANF. The ability of the factor to enhance cGMP levels was correlated with the distribution of particulate guanylate cyclase. This study identifies the glomeruli and the distal part of the nephron as specific targets of ANF and implicates particulate guanylate cyclase as the enzyme targetted for the expression of its action.
...
PMID:The increase of cGMP by atrial natriuretic factor correlates with the distribution of particulate guanylate cyclase. 285 57

The present study was undertaken to investigate the cAMP system in isolated vasopressin (AVP)-sensitive segments of the hypercalcemic rat. Hypercalcemia was produced by supplementation of diet with dihydrotachysterol, achieving a mean serum calcium of 12.6 mg%. Maximal urinary concentration was only 1982 +/- 119 mOsm/kg H2O in pair, watered hypercalcemic rats when compared to 2478 +/- 93 mOsm/kg H2O in controls (N = 7) (P less than 0.01). Vasopressin stimulated adenylate cyclase activity at concentrations of vasopressin between 10(-9) and 10(-7) M was indistinguishable in the outer medullary collecting duct (OMCD) and inner medullary collecting duct (IMCD) of tubules dissected from hypercalcemic rats or normocalcemic rats. Likewise, in situ cAMP accumulation in response to 10(-7) M AVP was not significantly different in either OMCD or IMCD of hypercalcemic or normocalcemic rats at either isotonic or hypertonic media conditions. In contrast, while 10(-7) M AVP significantly (P less than 0.05) increased cAMP accumulation in the medullary ascending limb (MAL) of normocalcemic rats it failed to do so in the MAL of hypercalcemic rats. This failure to accumulate cAMP appears to be due to impairment in AVP-stimulated adenylate cyclase rather than to enhanced phosphodiesterase activity. A similar decrement in glucagon stimulated adenylate cyclase occurred with 10(-6) M glucagon. The results demonstrate that in chronic hypercalcemia the cAMP system in the OMCT and IMCD of the rat is intact, but the MAL demonstrates abnormal AVP responsiveness due to impaired adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The cAMP system in vasopressin-sensitive nephron segments of the vitamin D-treated rat. 303 55

Mineralo- and glucocorticoid-deficient states, such as Addison's disease, are partly characterized by an inability to generate a maximally concentrated urine. The purpose of the present study was to develop a model of adrenal insufficiency and to determine whether changes in the intrinsic function of the collecting duct could partly account for this concentrating defect. Two kinds of experiments were performed: an assessment of the in vivo ability of adrenal-ectomized rabbits to concentrate their urine, and an examination of the intrinsic hydroosmotic responsiveness of in vitro perfused collecting ducts isolated from normal and adrenalectomized rabbits. The present study demonstrates that adrenalectomized rabbits are unable to concentrate their urine maximally, and that the in vivo administration of either deoxycorticosterone, 250 mug/kg, or dexamethasone, 50 mug/kg, restored to or toward normal their concentrating ability. When cortical collecting tubules from adrenalectomized rabbits were perfused in vitro, they demonstrated a markedly blunted hydroosmotic response to antidiuretic hormone (ADH), which was corrected by the in vitro addition of either aldosterone (50 pM) or dexamethasone (50 pM), but not progesterone (50 pM). The steroids by themselves, in the absence of ADH, had no intrinsic effect on the water permeability of the collecting duct. The blunted hydroosmotic response across cortical collecting tubules from adrenal-ectomized rabbits was corrected by the addition of either 8-bromo cyclic AMP or a potent phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine. The present studies show that the cortical collecting tubules obtained from adrenalectomized rabbits do not respond normally to ADH. The poor hydroosmotic response to ADH was corrected by exogenous aldosterone, dexamethasone, an analog of cyclic AMP, or a phosphodiesterase inhibitor. In conclusion, the present studies are consistent with the view that the concentrating defect seen in adrenal insufficiency is at least partly the result of the absence of the permissive effect that adrenal steroids exert on the ADH-induced reabsorption of water across the collecting duct. The absence of adrenal steroids results in a diminished rate of cyclic AMP accumulation in the cells of the collecting duct, either as a result of an augmented activity of cyclic AMP phosphodiesterase or a diminished rate of cyclic AMP generation.
...
PMID:Urinary concentrating defect of adrenal insufficiency. Permissive role of adrenal steroids on the hydroosmotic response across the rabbit cortical collecting tubule. 615 51

The papillary collecting duct (PCD) is considered to be of major importance in the final elaboration of the urine, but the metabolism of cyclic adenosine 3',5'-monophosphate (cAMP) has not yet been directly studied in the PCD. Therefore, in the present study we examined the basic properties of the cAMP system in isolated PCD microdissected from rat kidney. Vasopressin (VP) caused a marked (5- to 10-fold) stimulation of adenylate cyclase (AdC) but parathyroid hormone, calcitonin, isoproterenol, and bradykinin were without effect. A gradual increase in osmolality from 200 mosM had a biphasic effect on AdC, first enhancing (at 800 mosM) then inhibiting AdC activity at 2,000 mosM. cAMP-phosphodiesterase activity was inhibited as osmolality was increased from 200 to 800 mosM and the inhibition remained constant to 2,000 mosM. Incubation of intact PCD with VP resulted in a threefold increase in cAMP levels. As the osmolality of the incubation medium ws increased from 300 to 2,000 mosM, both basal and VP-stimulated cAMP levels continued to increase. Prostaglandin E2 (PGE2) (10(-5) M) alone (in the absence of vP) caused an increase in AdC activity, but the same dose of PGE2 had no effect on AdC activity stimulated by submaximal or maximal doses of VP. PGE2 (10(-5) M) caused a small increase in cAMP levels in intact PCD. On the other hand, PGE2 inhibited VP-stimulated cAMP levels by 50%. Incubation of PCD with PGE2 had no effect on cAMP-phosphodiesterase activity. The results demonstrate that osmolality in the physiologic range has a major influence on cAMP metabolism in the PCD and document an antagonism between PGE2 and VP at the level of cAMP accumulation in the PCD.
...
PMID:ADH-sensitive cAMP system in papillary collecting duct: effect of osmolality and PGE2. 626 88


1 2 3 4 5 Next >>

---