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: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasopressin analogues with enhanced antidiuretic activity in vivo (deamino-[D-arg8]-vasopressin, deamino-6-carba-[Orn8]-vasopressin, deamino-6-carba-[Arg8]-vasopressin, and deamino-6-carba-[D-Arg8]-vasopressin) were tested for their ability to activate rat renal medullary adenylate cyclase and compared to the natural antidiuretic hormones [Arg8]- and [Lys8]-vasopressin. The enzyme preparation used did not inactivate the vasopressins or the analogues tested. The analogues activated adenylate cyclase. However, several of them were far less effective than expected on the basis of their very high in vivo antidiuretic activity. It was concluded that the enhanced in vivo activity reflects greater metabolic stability in vivo rather than enhanced affinity for the renal antidiuretic hormone receptor.
...
PMID:Activation of rat kidney adenylate cyclase by vasopressin analogues: lack of correlation with antidiuretic activity. 114 17

The effect of the novel alpha-2 adrenoceptor agonist, AGN 190851, was evaluated for its diuretic action in the rat, dog and cynomolgus monkey and its ability to inhibit vasopressin-stimulated cyclic AMP accumulation in rat and dog cortical collecting tubules in vitro. The data indicate that in the rat, AGN 190851 resulted in a dose-dependent water diuresis, which was accompanied by an increase in blood pressure and osmolar clearance. In addition, AGN 190851 resulted in a dose-dependent inhibition of vasopressin-stimulated cyclic AMP accumulation in rat cortical collecting tubules in vitro. In contrast, AGN 190851 was unable to cause either a water diuresis in conscious dogs or inhibit vasopressin-stimulated adenylate cyclase activity in canine tissue in vitro. In the lightly anesthetized cynomolgus monkey, AGN 190851 also failed to alter renal function significantly. Administration of the vasopressin receptor antagonist, SK&F 105494, to either dogs or cynomolgus monkeys demonstrated that antagonism of the vasopressin V2 receptor could result in a brisk water diuresis in both species. The data demonstrate that alpha-2 adrenoceptors can functionally antagonize vasopressin antidiuretic activity in the rat, but not in the dog or cynomolgus monkey.
...
PMID:The water diuretic effect of the alpha-2 adrenoceptor agonist, AGN 190851, is species-dependent. 168 20

The signal transduction system of the vasopressin receptor in cerebral microvessels is not known but appears not to be adenylate cyclase/cyclic AMP. We determined the effect of arginine vasopressin (AVP) on the intracellular free calcium concentration [Ca2+]i in endothelial cells of isolated hippocampal microvessels of rats, using the fura-2 fluorescence technique. AVP administration caused a rapid and transient rise of cytosolic free calcium which was absent after extracellular calcium was removed, and could be blocked with the vasopressin V1 receptor antagonist, d(CH2)5 Tyr(Me)AVP. The vasopressin V2 receptor agonist, 1-deamino-8,D-AVP, on the contrary, failed to affect the intracellular free calcium level, and was unable to inhibit the AVP-induced rise of [Ca2+]i in the preparation. Our results, therefore, demonstrate the presence of a calcium-signalling, i.e. V1 vasopressin receptor at the blood-brain barrier in the hippocampus of the rat.
...
PMID:The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling. 183 82

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.
...
PMID:Desensitization of vasopressin sensitive adenylate cyclase by vasopressin and phorbol esters. 216 86

The lateral mobility of membrane integral receptors has been implicated as playing a significant role in signal transduction. The adenylate cyclase-coupled vasopressin V2 receptor has been shown to be highly laterally mobile in membranes of LLC-PK1 renal epithelial cells at physiological temperature using a fluorescent vasopressin agonist, with lateral mobility of the V2 receptor proposed to play a role in both adenylate cyclase activation and ligand induced receptor internalization and down-regulation. This study reports the synthesis and characterization of two new fluorescent antagonists [(beta-mercapto-beta,beta-cyclopentamethylene propionic acid)1,D-Tyr2,Ile4,Lys9(N6-fluoresceinylaminothiocarbonyl )]AVP (FL-AVP-anta) and [(beta-mercapto-beta,beta-cyclopentamethylene propionic acid)1,D-Tyr2,Ile4,Lys9(N6-tetramethylrhodamylaminothioca rbonyl)]AVP (TR-AVP-anta) for the V2 receptor. The latter was used to determine the parameters of lateral mobility of the V2 receptor in the non-activated antagonist-occupied form. Using fluorescence photobleaching techniques, results were largely comparable to those for agonist-occupied receptor, indicating high mobility at 37 degrees C. Antagonistic properties of the V2 receptor ligands are apparently not related to decreased receptor lateral mobility. Photobleaching measurements, however, did show that in contrast to V2 agonist, V2 antagonist did not induce receptor immobilization due to aggregation with time at 37 degrees C, indicating that this could be of mechanistic importance in the internalization process.
...
PMID:Lateral mobility of the antagonist-occupied V2 vasopressin receptor in membranes of renal epithelial cells. 808 94

Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder characterized by renal resistance to the antidiuretic hormonal action of arginine vasopressin. The disease gene has been assigned to the subtelomeric region of the X chromosome long arm by demonstrating close linkage between NDI and several X-chromosomal DNA markers. The finding of closely linked genetic markers is useful in the diagnosis of NDI. Receptor studies in patients have indicated that NDI might be due to the absence or an abnormality of the adenylate cyclase-bound vasopressin type 2 receptor. This assumption was supported by the discovery of functional vasopressin V2 receptor activity in somatic cell hybrid cell lines that carried at least the distal part of the human X chromosome long arm. Definite evidence for a V2 receptor defect being the cause of NDI was found in a recent study demonstrating point mutations in the V2 receptor gene from affected individuals. Direct mutation analysis is now applicable for accurate carrier detection and early (prenatal) diagnosis.
...
PMID:Nephrogenic diabetes insipidus: identification of the genetic defect. 825 44

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.
...
PMID:[Recent advances in vasopressin receptors and signal transduction system]. 825 35

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.
...
PMID:Separate receptors mediate oxytocin and vasopressin stimulation of cAMP in rat inner medullary collecting duct cells. 1008 3

X-Linked nephrogenic diabetes insipidus (NDI), which accounts for 90% of inherited cases of NDI, is caused by mutations in the AVPR2 gene that encodes the arginine vasopressin (AVP) receptor type 2 (V2R). The V2R mediates the antidiuretic action of AVP in principal cells of the collecting duct. To date, only three AVPR2 mutations (P322S, D85N, and G201D) have been associated with a mild NDI phenotype, and intrafamilial phenotype variability has not been reported in affected males. We describe a novel Belgian family with X-linked NDI caused by substitution of a histidine for an arginine at position 137 (R137H) of AVPR2. This mutation has been identified in two brothers and their mother. The R137H mutation results in a failure of V2R to stimulate adenylate cyclase and has been associated consistently with severe NDI and the inability to increase urinary osmolality to greater than plasma osmolality during water deprivation and/or infusion of 1-desamino-8-d-arginine vasopressin. Detailed examination of the two affected brothers showed the typical NDI phenotype in the 45-year-old proband, whereas a milder clinical phenotype associated with significant urinary concentrating ability during water deprivation was documented in the 33-year-old brother. Thus, in this family, the R137H mutation is associated with either a mild or severe NDI phenotype. Mechanisms that might account for these findings include genetic and/or environmental modifiers.
...
PMID:Intrafamilial phenotype variability in nephrogenic diabetes insipidus. 1192 Mar 39

In tetrapods, vasopressin (VP) and vasotocin (VT) are involved in various aspects of physiology and behavior including osmoregulation, cardiovascular function, reproduction, stress response and social behavior. Pharmacological and molecular studies have identified three types of VP/VT receptors, V1a-type (V1aR), V1b-type (V1bR) and V2-type (V2R). On the other hand, only V1aR has so far been identified in teleosts. In the present study, we successfully cloned V2Rs from two ray-finned fish, gray bichir and medaka. Phylogenetic analysis showed that the cloned receptors belong to the V2R group of lobe-finned fish and tetrapods. The amino acid sequences of bichir V2R and medaka V2R were high identity (60-65.5% and 53.2-80.9%, respectively) with other known V2R members, respectively. Reverse transcriptase PCR revealed that ray-finned fish V2R transcripts have been detected in various tissues including brain, gill, heart, liver, kidney and reproductive organs, suggesting that ray-finned fish V2R might mediate multiple functions of VT. In functional analysis, the cells transfected with the cloned receptors responded with the accumulation of intracellular cAMP in a concentration-dependent manner following VT stimulation, but not respond with [Ca(2+)]i. Furthermore, pretreatment with mammalian V2R antagonist (OPC-31260) to the cells transfected with medaka V2R significantly inhibited an increase of the VT-induced intracellular cAMP. These results suggest that ray-finned fish possess a functional V2R linked to adenylate cyclase and the cAMP signaling pathway as well as V2Rs of lobe-finned fish and tetrapods. Thus, the present study suggests that functional V2R evolved prior to the divergence of the ray- and lobe-finned fish lineages.
...
PMID:Molecular cloning and characterization of V2-type receptor in two ray-finned fish, gray bichir, Polypterus senegalus and medaka, Oryzias latipes. 2042 Aug 73


1 2 Next >>

---