Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat inner medullary collecting tubule (RIMCT) cells produce arachidonate derivatives including prostacyclin (PGI2). In RIMCT cells, PGI2 causes a dose-dependent increase in adenosine 3',5'-cyclic monophosphate (cAMP; fmol/micrograms protein) from a basal level of 15.6 +/- 1.7 to 32.4 +/- 5.7 at 0.3 microM, 63.3 +/- 8.3 at 3 microM, and 103.5 +/- 9.4 at 30 microM PGI2. At concentrations of arginine vasopressin (AVP) from 10(-7) to 10(-9) M, cAMP was greater in the presence than absence of 3 microM PGI2, suggesting independent sites of action. To assess whether the PGI2 effect is mediated by the prostaglandin E2 (PGE2) receptor, desensitization studies were performed. A 6-h preincubation with 10 microM PGE2 blunted the response to 3 microM PGE2 by 90 +/- 2% but the PGI2 response was decreased by only 31 +/- 5%, P less than 0.001. Carbaprostacyclin (carba-PGI2), a stable analogue of PGI2, blunted the cAMP response to PGI2 by 94 +/- 3% but to PGE2 by only 46 +/- 7%, P less than 0.005. The postreceptor effect of PGI2 on components of the adenylate cyclase was examined. The response to forskolin was markedly potentiated by PGI2. PGI2 (3 microM) caused an increase in cAMP of 67 fmol/micrograms over basal in the absence of forskolin, of 164 fmol/micrograms at 10(-7) M forskolin, of 386 fmol/micrograms at 10(-6) M forskolin, and of 563 fmol/micrograms at 10(-5) M forskolin. The response of PGI2 was likewise potentiated by forskolin. Water permeability alone or in response to AVP in isolated perfused inner medullary collecting tubules was not affected by carba-PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of prostacyclin on the cAMP system in cultured rat inner medullary collecting duct cells. 215 16

The present study was undertaken to determine whether the absence of extracellular Na+ affects cellular action of arginine vasopressin (AVP) in rat renal inner medullary collecting duct cells in culture. AVP increased cellular cAMP production in a dose-dependent manner. Na+ depletion promptly diminished the cellular cAMP response to AVP (1 nM AVP; 405.9 +/- 26.1 vs. 189.8 +/- 12.1 fmol/micrograms protein, P less than 0.01). The dose-response relation shifted to the right. The inhibition of the ability of AVP to produce cAMP was observed with an extracellular Na+ concentration less than 60 mM. Similar results were obtained with 2 x 10(-8) M forskolin, a diterpene activator of adenylate cyclase. Such inhibition was easily released, since only 10-min reexposure of the Na(+)-depleted cells to the control medium totally recovered the cAMP response to AVP. Extracellular Na+ depletion promptly decreased the cellular Na+ concentration from 15.8 +/- 1.0 to 5.4 +/- 0.6 mM (P less than 0.01), measured using the fluorescence dye sodium-binding benzofuran isophthalate. If the Na(+)-depleted cells were again incubated with the control medium, intracellular Na+ rapidly recovered to the precontrol level. Such a change was closely related to the change in cellular pH, which decreased from 7.19 +/- 0.02 to 6.97 +/- 0.02, measured using the fluorescence dye 2',7'-bis-(2-carboxymethyl)-5 (and -6)carboxyfluorescein,acetamethylester. However, Na+ depletion did not affect the cellular free calcium concentration or cellular protein and ATP contents. These results indicate that Na+ depletion promptly attenuated the ability of AVP to produce cAMP mediated through either the decrease in intracellular Na+ or cellular pH in renal inner medullary collecting duct cells.
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PMID:Prompt inhibition of arginine vasopressin-induced cellular adenosine 3',5'-monophosphate production by extracellular sodium depletion in rat renal inner medullary collecting duct cells in culture. 216 12

It is well known that prostaglandin E2 (PGE2) both inhibits arginine vasopressin (AVP)-stimulated water permeability (hydraulic conductivity, Lp) in the cortical collecting duct (CCD) or, if administered alone, modestly increases Lp in the CCD. These bifunctional effects on Lp correspond to PGE2's capacity to inhibit AVP-stimulated adenylate cyclase (AC) activity, or to singularly stimulate AC activity in the collecting duct. The present studies suggest that the inhibitory effect of PGE2 on Lp may also be mediated by phosphatidylinositol (PI) hydrolysis. Using in vitro microperfused rabbit CCDs, we show that PGE2 releases Ca from intracellular stores. We also demonstrate that the inhibitory effect of PGE2 on AVP-stimulated Lp in the CCD is significantly reversed by the protein kinase C (PKC) inhibitor, staurosporine (SSP). Although PGE2 does not reduce an established water flow response to 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (8-CPTcAMP), when the sequence of addition is reversed and PGE2 is added first, marked inhibition of 8-CPTcAMP-induced Lp is observed. This provides independent evidence that PGE2 can act through a mechanism separate from modulating AC activity. PGE2 inhibition of 8-CPTcAMP-induced Lp is reversed by SSP pretreatment. Finally, SSP pretreatment also markedly potentiates the capacity of PGE2 itself to increase Lp. We conclude that PGE2 releases Ca from intracellular stores and, by activating PKC, inhibits AVP-induced osmotic water flow. This suggests an important role for PI hydrolysis in mediating PGE2's effects on the CCD.
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PMID:PGE2 inhibits AVP-induced water flow in cortical collecting ducts by protein kinase C activation. 216 17

Desensitization of vasopressin V2 receptor-mediated adenylate cyclase was studied in canine kidney cell line, MDCK cells. Overnight treatment of MDCK cells with arginine vasopressin (AVP) resulted in a loss of vasopressin receptors and an inhibition of cAMP accumulation in response to AVP. Both the loss of receptor and reduction in cAMP accumulation were time- and AVP concentration-dependent. Desensitization was selective for AVP because cAMP formation in response to isoproterenol, prostaglandin E1 (PGE1) and forskolin was not affected by AVP pre-treatment. Pre-treatment of MDCK cells with phorbol dibutyrate (PDBu) also caused a dose-dependent inhibition of AVP mediated cAMP accumulation, but not of isoproterenol-, PGE1- and forskolin-induced cAMP accumulation. PDBu pre-treatment did not cause loss of vasopressin receptors. Instead, the affinity for vasopressin was changed by PDBu treatment. Pre-treatment of the cells with pertussis toxin (PT) had no effect on the desensitization and downregulation of vasopressin (V2) receptors, suggesting that the desensitization may not be mediated by pertussis toxin sensitive G-protein. Our data suggest that pre-treatment of MDCK cells with AVP or PDBu caused desensitization of AVP-mediated cAMP accumulation and that downregulation of V2 receptors required agonist occupancy of the receptors, whereas the affinity of the receptors was changed by phorbol ester treatment.
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PMID:Desensitization of vasopressin sensitive adenylate cyclase by vasopressin and phorbol esters. 216 86

To study vasopressin receptor-mediated endocytosis using electronmicroscopy methods and to develop avidin affinity columns for receptor purification, we synthesized and tested the biological properties of a biotinylated vasopressin (VP) analog [1-(2-mercapto) propionic acid] 8-[lysine-N6-biotin] VP (B-MLVP). B-MLVP was prepared by coupling biotin to the epsilon amine of the lysine residue in [1-(2-mercapto) propionic acid] 8-(lysine) VP (MLVP). The structure of HPLC purified B-MLVP was confirmed by fast atom bombardment mass spectrometry. B-MLVP effectively competed for arginine vasopressin (AVP) binding sites in canine renal plasma membranes on the surface of LLC-PK1 kidney cells. Dissociation constants of 15 nM and 202 nM were calculated from the results of competition binding assays conducted with membranes and cells, respectively. B-MLVP stimulated adenylate cyclase activity and elevated cellular 3',5',cyclic-AMP (cAMP) content in a manner similar to AVP, indicating it is an agonist of VP action in renal tissue. These observations indicate that B-MLVP is an agonist of VP action and may be used to study renal VP receptors by employing avidin coupled to various reporter groups.
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PMID:Synthesis and biological activity of a biotinylated vasopressin analog. 217 38

Arginine vasopressin (AVP) acts on at least two receptor types, classified on the basis of their second messengers. The V1 receptor acts via mobilization of intracellular calcium through phosphatidylinositol hydrolysis and influences blood pressure and hepatic glycogenolysis. The V2 receptor acts via cAMP through activation of adenylate cyclase and causes antidiuresis. Previous studies of the different AVP receptors have been hampered by the use of nonselective radioligands, such as [3H]AVP (which binds to all types of V1 and V2 receptors, certain oxytocin receptors, and neurophysins) as well as the difficulty of measurement of second messengers. This paper describes the use of selective V1 and V2 radioligands with in vitro autoradiography to study V1 and V2 binding sites in rat tissues. [125I][1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 7-sarcosine] arginine vasopressin ([125I][d(CH2)5,Sarcosine7]AVP), a selective V1 antagonist radioligand, bound to regions of the brain, testis, superior cervical ganglion, liver, blood vessels, and renal medulla. Pharmacological characterization of [125I][d(CH2)5,Sarcosine7]AVP binding was consistent with that expected for binding to V1 receptors. There was no specific binding demonstrable to pituitary, renal glomeruli, gut, heart, spinal cord, ovary, adrenal medulla, or adrenal cortex. [3H]1-deamino [8-D-arginine] vasopressin [( 3H]DDAVP), a potent V2 receptor agonist radioligand, was used to study V2 receptors. Specific binding was only identified in the kidney consistent with the known distribution of antidiuretic V2 receptors on renal collecting tubules. No binding was demonstrated on endothelium or liver where DDAVP might influence clotting factor release, nor in the brain, spinal cord, sympathetic ganglia, heart or vascular smooth muscle, regions where DDAVP might cause vasodilatation. These studies demonstrate the use of these radioligands to study V1 and V2 receptors in a variety of tissues. Also, since these ligands are selective they are of particular use to study the different receptor subtypes in tissues where V1 and V2 receptors coexist, such as in the kidney.
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PMID:Localization of vasopressin binding sites in rat tissues using specific V1 and V2 selective ligands. 230 15

To elucidate the mechanism generating bursting activity, the effect of arginine vasopressin (AVP) was studied electrophysiologically and biochemically in ganglionic preparations from the snail, Euhadra peliomphala. AVP caused bursting activity which is accompanied by the development of a negative slope resistance (NSR) region in the current-voltage (I-V) curve of the identified neurons. Similar effects were observed by application of veratridine, dibutyryl cyclic AMP and isobutylmethylxanthine. Both the bursting activity and the I-V relation induced by AVP were markedly inhibited by reduction of extracellular Na+ but not by Co2+-substituted Ca2+-free saline. This hormone also caused the following intracellular biochemical alterations: elevation in the cyclic AMP levels; stimulation of adenylate cyclase and Ca2+-dependent protein kinase activities; and promotion of Ca2+ release from the intracellular reservoir, lysosome-like granules. These results suggest that AVP-induced bursting activity is mediated through intracellular biochemical processes.
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PMID:Membrane properties and intracellular biochemical processes during vasopressin-induced bursting activity in snail neurons. 243 48

Although guanosine 3',5'-cyclic monophosphate (cGMP) is present in renal nephron segments, there is no information on the role of cGMP as a mediator of renal tubular transport events. We found that an activator of guanylate cyclase (nitroprusside) and 8-bromocGMP (8-BrcGMP) significantly increased hydraulic conductivity in rabbit and rat cortical collecting tubules (CCT) perfused in vitro. The effect of 10(-4) M 8-BrcGMP to increase CCT hydraulic conductivity was reversible and comparable in magnitude and time course to that produced by maximal concentrations of arginine vasopressin. In rabbit CCT, cGMP increased hydraulic conductivity in the presence of phosphodiesterase inhibition with methylisobutylxanthine and in the presence of supramaximal concentrations of arginine vasopressin. Neither nitroprusside nor 8-BrcGMP stimulated adenylate cyclase activity in microdissected CCT. These data demonstrate that cGMP can act independently of either stimulation of adenylate cyclase activity or inhibition of phosphodiesterase activity to increase hydraulic conductivity in the mammalian CCT.
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PMID:Cyclic guanosine monophosphate increases hydraulic conductivity in rabbit and rat CCT. 246 Oct 96

The effects of arginine vasopressin (AVP) on the cytosolic free calcium concentration ([Ca2+]f) were examined in freshly immunodissected rabbit cortical collecting tubule cells using fluorescent Ca2+ indicators fura-2 and indo-1. The addition of AVP to a cell suspension resulted in a rapid and transient increase in the [Ca2+]f. The 1-deamino-8-D-AVP (dDVP), a V2 receptor agonist of AVP that stimulated adenosine 3',5' cAMP production in these cells, had no effect on [Ca2+]f and did not affect AVP-induced increase in [Ca2+]f. The AVP-induced increase in [Ca2+]f but not cAMP production was blocked by the V1 receptor antagonist, [1-(beta-mercapto-beta-beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] Arg8-vasopressin. The AVP-stimulated increase in [Ca2+]f appeared to be largely due to Ca2+ release from intracellular stores as reduction of extracellular Ca2+ with EGTA had little if any effect on the AVP-induced increase in [Ca2+]f. This AVP-induced increase in [Ca2+]f was associated with an increase in inositol-1,4,5-trisphosphate production and appeared to involve a guanine nucleotide-binding protein (G), since the pretreatment of cells with pertussis toxin for 4-6 h inhibited this effect. Finally, measurements of [Ca2+]f in single cells suggest that only the principal cells of the collecting tubules respond to AVP with an increase in [Ca2+]f. In summary, these results demonstrate that the principal cells of the cortical collecting tubule possess two distinct receptor systems for vasopressin, the well-known V2 receptor coupled to adenylate cyclase, and a V1 receptor system that leads to the mobilization of cytosolic calcium, coupled through a pertussis toxin substrate (G protein) to a production of inositol phosphates.
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PMID:Vasopressin V1 receptors on the principal cells of the rabbit cortical collecting tubule. Stimulation of cytosolic free calcium and inositol phosphate production via coupling to a pertussis toxin substrate. 253 47

Atrial natriuretic factor (ANF) has been suggested to exert a tubular effect on the mammalian nephron, perhaps in part by interacting with other hormones. In the present study, the effect of ANF was examined on glomeruli (Gm) and different renal tubule segments including medullary (MAL) and cortical thick ascending limb (CAL) and cortical (CCT), outer medullary (OMCT) and inner medullary collecting tubules (IMCT). This effect of ANF was assessed by alteration in adenylate cyclase and cGMP in the various nephron segments in the presence and absence of arginine vasopressin (AVP), parathyroid hormone (PTH) and calcitonin (SCT). An effect of ANF (10(-8) M) was not demonstrated on adenylate cyclase (fmol cAMP formed/30 min/micrograms protein) in Gm, CAL, MAL, CCT, OMCT or IMCT. Nor did ANF (10(-8) M) interfere with the effect of PTH (5 IU/ml) on the Gm (PTH 35.1 +/- 3.7 vs. PTH + ANF 32.5 +/- 1.8, NS), CAL (PTH 50.5 +/- 10.9 vs. PTH + ANF 46.2 +/- 1.4, NS) or AVP (10(-8) M) on the CCT (AVP 40.8 +/- 6.6 vs. AVP + ANF 33.0 +/- 3.1, NS), OMCT (AVP 56.0 +/- 11.8 vs. AVP + ANF 42.1 +/- 6.7, NS), IMCT (AVP 66.5 +/- 4.6 vs. AVP + ANF 53.5 +/- 7.0, NS) or MAL (AVP 15.5 +/- 1.6 vs. AVP + ANF 14.0 +/- 2.6, NS). ANF also did not affect SCT (1.5 x 10(-8) M)-induced adenylate cyclase on CCT (SCT 69.8 +/- 11.3 vs. SCT + ANF 79.9 +/- 7.2, NS). ANF (10(-8) M), however, significantly increased cGMP in the Gm (6.4 +/- 1.7 to 121.3 +/- 32.4 fmol/micrograms protein, P less than 0.001) and IMCT (0.63 +/- 0.16 to 1.46 +/- 0.29 fmol/micrograms protein, P less than 0.05). However, no effect of ANF on cGMP was observed in the CAL, CCT, OMCT, and MAL even at 10(-7) M ANF. PTH (5 IU/ml) did not alter either basal or ANF-stimulated cGMP in the Gm. Also, specific ANF binding was studied in the microdissected IMCT. Kd was 6.08 x 10(-9) M and Bmax was 8.07 x 10(-11) M.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzymatic and binding effects of atrial natriuretic factor in glomeruli and nephrons. 254 Mar 77


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