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)

The effect of prostaglandin I2 (prostacyclin) on renal and intrarenal hemodynamics and function was studied in mongrel dogs to elucidate the role of this novel prostaglandin in renal physiology. Starting at a dose of 10(-8) g/kg/min, PGI2 decreased renal vascular resistance and redistributed the blood flow away from the outer cortex (zone 1) and towards the juxtamedullary cortex (zone 4). At 3 X 10(-8) g/kg/min, the renal vascular resistance decreased even further, but at this dose the mean arterial blood pressure also declined 13% indicating recirculation of this prostaglandin. PGI2 infusion at a vasodilatory dose resulted in natriuresis and kaliuresis. With a decline in filtration fraction, these changes were most likely secondary to the hemodynamic effects of this prostaglandin. Unlike PGE2, PGI2 had no direct effect on free water clearance indicating lack of activity at the collecting duct. PGI2 may be the important renal prostaglandin involved in modulating renal vascular resistance and intrarenal hemodynamics as well as influencing systemic blood pressure.
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PMID:The effect of PGI2 on canine renal function and hemodynamics. 36 49

The effects of prostaglandin (PG) E2 on cell swelling were studied in isolated perfused tubules of rabbit kidney. PGE2 (1 microM) added to the bath induced cell swelling by 13.4, 7.2, and 9.6% in the connecting tubule, distal convoluted tubule, and cortical collecting duct, respectively, but it had no effect on the proximal convoluted tubule and cortical thick ascending limb. The response was dose dependent in the range of 1 nM to 1 microM. PGI2 exerted a similar effect, but PGF2 alpha had no effect. The swelling was completely blocked by basolateral Na+ removal and was attenuated by bilateral Cl- removal, suggesting that the swelling was mediated by basolateral Na+ entry in association with Cl- entry. In all segments except proximal tubule, PGE2 caused an initial transient peak followed by a sustained increase in intracellular Ca2+. Intracellular Ca2+ chelation or inhibition of Ca2+ release from intracellular stores abolished the PGE2-induced cell swelling, but extracellular Ca2+ removal did not. An inhibitor of the Na(+)-Ca2+ exchanger (3',4'-dichlorobenzamil, 100 microM) in the bath completely inhibited PGE2-induced cell swelling. Neither furosemide (1 mM) nor amiloride (1 mM) added to bath abolished the response, indicating that neither Na(+)-K(+)-2Cl- cotransport nor Na(+)-H+ exchange is involved in the action of PGE2. The swelling response to PGE2 was observed even in the presence of ouabain, indicating that the effect of PGE2 is independent of Na(+)-K(+)-adenosinetriphosphatase inhibition. Nicardipine added to bath partially inhibited the swelling response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of PGE2-induced cell swelling in distal nephron segments. 133 3

Renal prostaglandins (PGs) help maintain renal blood flow and glomerular filtration rate when the kidney is exposed to a vasoconstrictor stress. In addition, they aid pressure natriuresis and blunt the antidiuretic effect of vasopressin. Angiotensin-converting enzyme (ACE) inhibitors could decrease renal PG synthesis by reducing angiotensin II (Ang II) formation or increase it by preventing kinin inactivation. Additionally, they could affect PG synthesis or catabolism directly. The effects of ACE inhibitors on blood pressure and renal hemodynamics appear to be largely independent of changes in renal PG synthesis. Similarly, there is no evidence that pressure natriuresis is modified by ACE inhibitors. A kinin induced increase in collecting duct PG synthesis may account for the water diuresis seen clinically with ACE inhibitors. A possible beneficial interaction between thromboxane synthesis inhibitors and ACE inhibitors may exist. Thromboxane synthetase inhibitors can reduce renal vascular resistance by redirecting PG endoperoxide synthesis toward prostacyclin. This effect may be offset by a prostaglandin-induced increase in renin release and Ang II formation. ACE inhibitors, by preventing Ang II synthesis, may increase the vasodilation due to thromboxane synthesis inhibition.
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PMID:Renal prostaglandin synthesis and angiotensin-converting enzyme inhibition. 138 64

Prostaglandin E2 (PGE2) inhibits vasopressin-stimulated water conductivity (AVP-Lp) and inhibits Na+ reabsorption in the rabbit cortical collecting duct (CCD). Inhibition of Na+ reabsorption is mediated by increased intracellular calcium ion concentration ([Ca2+]i). Prostacyclin (PGI2) has also been shown to inhibit Na+ reabsorption in the CCD. The present studies were designed to examine the effect of the PGI2 agonist, Iloprost (ILP), on AVP-Lp and [Ca2+ in the isolated perfused rabbit CCD and to determine whether ILP activates different receptors than PGE2. ILP and PGE2 each maximally inhibited AVP-Lp equipotently at 10(-7) M. When CCDs were exposed to PGE2 and ILP simultaneously, or if PGE2 was added in the presence of ILP, inhibition of AVP-Lp was additive. Additivity was not observed if the PGI2 agonist, carbaprostacyclin (c-PGI2), was added with ILP, or if the PGE2 agonist, sulprostone, was added with PGE2, or if ILP was added to CCDs preexposed to PGE2. In fura 2-loaded CCD, ILP and PGE2 added separately increased [Ca2+]i. The response to c-PGI2 could be desensitized by prior exposure to ILP. ILP did not cause desensitization to PGE2, but PGE2 could desensitize the CCD to ILP. We conclude that PGI2 inhibits AVP-Lp by activation of a novel IP3 prostacyclin receptor and increases [Ca2+]i by activation of an IP1 prostacyclin receptor in the rabbit CCD. Functional evidence is presented that PGI2 cannot occupy PGE2 receptors and that PGE2 can occupy but cannot activate PGI2 receptors linked to inhibition of AVP-Lp.
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PMID:Rabbit cortical collecting ducts express a novel prostacyclin receptor. 753 Sep 13

Endothelins (ET) possess both vasodilatory and vasoconstrictive properties. The renal actions of ET-1 and ET-3, as well as in vivo interactions of these two isopeptides with the prostaglandin and endothelium-derived relaxation factor/nitric oxide systems were studied in anesthetized dogs. The ETs were infused intrarenally at doses not affecting systemic hemodynamics. Both ET-1 and ET-3 induced an early transient renal vasodilation, followed by a prolonged vasoconstriction. Inhibition of nitric oxide synthase with NG-monomethyl-L-arginine completely abolished the renal vasodilation induced by either ET-1 or ET-3 and enhanced the vasoconstriction. Endothelin-1 was associated with an increase in the renal release of prostacyclin, while urinary thromboxane A2 was increased after ET-3 administration. Inhibition of cyclooxygenase (with indomethacin) augmented the renal vasoconstriction induced by ET-1, but inhibition of cyclooxygenase (with meclofenamate) abolished the ET-3-evoked vasoconstriction. Endothelin-1 showed little effects on urinary water and sodium excretion; however, ET-3 displayed significant diuretic and natriuretic effects, which were inhibited by nitric oxide synthase inhibition. These findings suggest that these two isopeptides activate the endothelial endothelium-derived relaxation factor/nitric oxide system, which elicits early renal vasodilation, whereas direct effects on the vascular smooth muscle leads to vasoconstriction. Endothelin-3 causes diuresis and natriuresis, possibly by inducing release of nitric oxide in medullary collecting duct cells.
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PMID:Renal actions of endothelin-1 and endothelin-3: interactions with the prostaglandin system and nitric oxide. 754 37

We have previously found that arginine vasopressin (AVP) acts not only from the basolateral side but also from the luminal side of the rabbit cortical collecting duct (CCD). In the present study, we examined whether prostaglandin E2 (PGE2), another classic and potent modulator of the collecting duct functions, exerts luminal actions in the rabbit CCD perfused in vitro. Although luminal prostaglandin I2 was inert, luminal PGE2 (> 1 nM) induced transient hyperpolarization of transepithelial voltage followed by sustained depolarization in a dose-dependent manner. This action was preserved in the presence of basolateral PGE2, luminal AVP, or luminal BaCl2, but abolished by basolateral ouabain or luminal amiloride. Furthermore, unlike luminal AVP, luminal PGE2 suppressed Na transport and increased osmotic water permeability. The present study suggests that PGE2, similar to AVP but in a different fashion, modulates transepithelial transports from both luminal and basolateral sites in the CCD in vivo.
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PMID:Luminal prostaglandin E2 modulates sodium and water transport in rabbit cortical collecting ducts. 761 50

Renal cyclooxygenase-1 and cyclooxygenase-2 actively metabolize arachidonate to metabolism five primary prostanoids: prostaglandin E2, prostaglandin F2a, prostaglandin I2, thromboxane A2, and prostaglandin D2. These lipid mediators interact with a family of distinct G-protein-coupled prostanoid receptors designated EP, FP, IP, TP, and DP, respectively, which exert important regulatory effects on renal function. The intrarenal distribution of these prostanoid receptors has been mapped and the consequences their activation are being characterized. The FP, TP, and EP1 receptors preferentially couple to increased cell Ca2+. EP2, EP4, DP, and IP receptors stimulate cyclic adenosine monophosphate, whereas the EP3 receptor preferentially couples to Gi, inhibiting cyclic adenosine monophosphate generation. EP1 and EP3 messenger RNA expression predominate in the collecting duct and thick limb, respectively, where their stimulation reduces sodium chloride and water absorption, promoting natriuresis and diuresis. Interestingly, only a mild change in renal water handling is seen in the EP3 receptor knockout mouse. Although only low levels EP2 receptor messenger RNA are detected in kidney and its precise intrarenal localization is uncertain, mice with targeted disruption of the EP2 receptor display salt-sensitive hypertension, suggesting it also plays an important role in salt excretion. In contrast, EP4 messenger RNA is readily detected in the glomerulus where it may contribute to the regulation of renin release and decrease glomerular resistance. TP receptors are also highly expressed in the glomerulus, where they may increase glomerular vascular resistance. The IP receptor messenger RNA is most highly expressed in the afferent arteriole and it may also modulate renal arterial resistance and renin release. At present there is little evidence for DP receptor expression in the kidney. Together these receptors act as physiologic buffers that protect the kidney from excessive functional changes during periods of physiologic stress. Loss of the combined effects of these receptors contributes to the side effects seen in the setting of nonsteroidal anti-inflammatory drug administration, whereas selective antagonists for these receptors may provide new therapeutic approaches in disease.
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PMID:Prostaglandin receptors: their role in regulating renal function. 1065 21

Renal cyclooxygenase 1 and 2 activity produces five primary prostanoids: prostaglandin E2, prostaglandin F2alpha, prostaglandin I2, thromboxane A2, and prostaglandin D2. These lipid mediators interact with a family of distinct G protein-coupled prostanoid receptors designated EP, FP, IP, TP, and DP, respectively, which exert important regulatory effects on renal function. The intrarenal distribution of these prostanoid receptors has been mapped, and the consequences of their activation have been partially characterized. FP, TP, and EP1 receptors preferentially couple to an increase in cell calcium. EP2, EP4, DP, and IP receptors stimulate cyclic AMP, whereas the EP3 receptor preferentially couples to Gi, inhibiting cyclic AMP generation. EP1 and EP3 mRNA expression predominates in the collecting duct and thick limb, respectively, where their stimulation reduces NaCl and water absorption, promoting natriuresis and diuresis. The FP receptor is highly expressed in the distal convoluted tubule, where it may have a distinct effect on renal salt transport. Although only low levels of EP2 receptor mRNA are detected in the kidney and its precise intrarenal localization is uncertain, mice with targeted disruption of the EP2 receptor exhibit salt-sensitive hypertension, suggesting that this receptor may also play an important role in salt excretion. In contrast, EP4 receptor mRNA is predominantly expressed in the glomerulus, where it may contribute to the regulation of glomerular hemodynamics and renin release. The IP receptor mRNA is highly expressed near the glomerulus, in the afferent arteriole, where it may also dilate renal arterioles and stimulate renin release. Conversely, TP receptors in the glomerulus may counteract the effects of these dilator prostanoids and increase glomerular resistance. At present there is little evidence for DP receptor expression in the kidney. These receptors act in a concerted fashion as physiological buffers, protecting the kidney from excessive functional changes during periods of physiological stress. Nonsteroidal anti-inflammatory drug (NSAID)-mediated cyclooxygenase inhibition results in the loss of these combined effects, which contributes to their renal effects. Selective prostanoid receptor antagonists may provide new therapeutic approaches for specific disease states.
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PMID:G protein-coupled prostanoid receptors and the kidney. 1118 68

The prostacyclin (IP) message was detected by RT-PCR in the renal cortex, outer (OM) and inner medulla (IM), and in freshly isolated (IMCD-f) and cultured inner medullary collecting duct (IMCD-c), and also the E-prostanoid (EP)1,3,4 receptor subtypes, but not EP2. Digoxigenin in situ hybridization localized IP mRNA in the tubules of the OM and IM, and the vasculature, and also in the glomeruli, arteries, and tubules of the cortex. IP splice variants or subtypes could not be detected by RT-PCR followed by TA cloning, though several nonfunctional point mutations or single base pair deletions were observed. Iloprost (ILP), cicaprost (CCP), PGE2, and arginine vasopressin (AVP) stimulated cAMP in both IMCD preparations. In addition, AVP-stimulated cAMP in IMCD-f was inhibited by all three prostanoids, but not in IMCD-c. Calcium experiments were performed on IMCD-c or microdissected IMCD (IMCD-m). CCP, ILP, and PGE2 did not alter intracellular calcium concentration ([Ca2+]i) in IMCD-c. However, on IMCD-m, both PGE2 and ILP increased [Ca2+]i levels equipotently and CCP had no effect. Pretreatment with the EP1 antagonist AH-6809 indicates that the response to ILP and PGE2 is mediated via EP1. These results suggest that IP receptors in the rat IMCD mediate the cAMP but not calcium signaling linked to PGI2; to date no subtypes or splice variants have been identified.
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PMID:Molecular and biochemical characterization of prostacyclin receptors in rat kidney. 1120 2

The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 +/- 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI(2)), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 +/- 0.15 to 1.8 +/- 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 +/- 0.2 to 1.8 +/- 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 +/- 0.12 vs. 3.15 +/- 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI(2) analogue, iloprost, can induce U-AQP2 excretion independent of AVP.
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PMID:Effect of a prostacyclin analogue, iloprost, on urinary aquaporin-2 excretion in humans. 1205 53


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