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)

We conducted this study to determine what receptor mediates the effect of oxytocin to increase osmotic water permeability (Pf) in the rat inner medullary collecting duct (IMCD). Reverse transcription-polymerase chain reaction (RT-PCR) experiments demonstrated that mRNA for both the oxytocin receptor and the V2 receptor is present in the rat terminal IMCD. In isolated perfused IMCD segments, we found that the V2 vasopressin receptor antagonist [d(CH2)5(1),D-Ile2,Ile4,Arg8]vasopressin, but not oxytocin receptor antagonists, blocked the hydrosmotic response to 200 pM oxytocin. The selective oxytocin receptor agonist [Thr4,Gly7]oxytocin did not increase water permeability. Oxytocin also increased urea permeability in IMCD segments. Studies in IMCD suspensions showed that oxytocin increases adenosine 3',5'-cyclic monophosphate production in a dose-dependent fashion with a half-maximal (EC50) response at 5.2 nM. The dose-response curves were virtually identical for IMCD suspensions from Sprague-Dawley rats and Brattleboro rats. The oxytocin dose-response curve was displaced to the right of the vasopressin dose-response curve (EC50, 0.44 nM). From these results, we conclude that the V2 receptor mediates the hydrosmotic action of oxytocin in rat IMCD.
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PMID:Oxytocin as an antidiuretic hormone. II. Role of V2 vasopressin receptor. 763 34

In renal collecting duct epithelial cells, arginine vasopressin (AVP) at greater than nanomolar concentrations has been reported to transiently increase intracellular free calcium ([Ca2+]i) in a manner consistent with activation of the phosphoinositide pathway. To investigate whether any of the known neurohypophysial hormone subtypes are involved, we measured [Ca2+]i in microdissected rat terminal inner medullary collecting duct (IMCD) using fura-2. To allow quantitative comparisons of the response under different conditions, we determined the areas under the response curves (in nM.min) over 1.5 min using numerical integration. AVP, the V1b-receptor agonist [deamino1,D-3-(pyridyl)Ala2,Arg8]vasopressin, the V2-receptor agonist 1-desamino-8-D-arginine vasopressin, oxytocin, and the selective oxytocin-receptor agonist [Thr4,Gly7]oxytocin (TG-OXT), each at 10 nM, significantly increased [Ca2+]i (69.52 +/- 10.25, 27.0 +/- 11.7, 24.33 +/- 5.83, 14.75 +/- 2.81, and 14.57 +/- 3.50 nM.min, respectively). In contrast, a V1a-selective agonist ([Phe2,Ile3,Orn8]vasopressin) did not increase [Ca2+]i (0.43 +/- 2.36 nM.min). In desensitization studies, challenge with 10 nM AVP or TG-OXT completely prevented a rise in [Ca2+]i in response to immediate rechallenge with the same agent, but not the other, demonstrating homologous desensitization. The lack of cross-desensitization implies that at least two receptors are present that can trigger a rise in [Ca2+]i in response to neurohypophysial hormones. Antagonists for oxytocin ([des-glycinamide9,d(CH2)5(1),O-Me-Tyr2,Thr4,Orn8]vaso tocin), V2 ([d(CH2)5(1),D-Ile2,Ile4,Arg8]vasopressin), and V1a ([d(CH2)5(1),O-Me-Tyr2,Arg8]vasopressin) receptors partially inhibited the [Ca2+]i response induced by 10 nM AVP (89.5, 81.6, and 51.4% inhibition, respectively). These data are consistent with the view that both an oxytocin receptor and a vasopressin receptor are coupled to a [Ca2+]i mobilization response in rat terminal IMCD. This vasopressin receptor is distinct from both the V1a receptor and the V2 receptor and may be either the V1b receptor or a novel vasopressin receptor subtype.
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PMID:Vasopressin and oxytocin receptors coupled to Ca2+ mobilization in rat inner medullary collecting duct. 839 22

The oxytocin and the vasopressin V1a, V1b and V2 receptors have recently been cloned and shown to form a sub-family within the large superfamily of G-protein-linked receptors. Renal V2 receptors mediate vasopressin-induced water reabsorption via induction of intracellular cAMP production in collecting duct cells. Most remaining actions of vasopressin on blood vessel constriction, liver glycogenolysis, platelet adhesion, adrenal angiotensin II secretion and certain brain functions are mediated via v1a-type receptors that are coupled to a Gq/11 protein. V1 receptor activation leads to stimulation of phospholipases C, D and A2 and an increase in intracellular calcium. Vasopressin stimulates pituitary corticotrophin release via a third vasopressin receptor type (V1b) which is present on corticotrophs. Oxytocin induces myometrial contraction, endometrial prostaglandin F2 alpha production, mammary gland milk ejection, renal natriuresis and specific sexual, affiliative and maternal behaviours via oxytocin receptors which are also coupled to a Gq/11 protein. Although only one oxytocin receptor type has been cloned so far, recent binding studies indicate that uterine endometrial oxytocin receptors may constitute a distinct receptor subtype. In contrast to most other membrane receptors, the expression of oxytocin receptors undergoes very rapid and physiologically relevant up-and-down-regulation. A > 100-fold up-regulation of uterine oxytocin receptors occurs during gestation and may represent the trigger for parturition. Indeed, oxytocin receptor antagonists are able to counteract preterm labour and may soon be available for clinical use. The presence of oxytocin receptors on breast cancer cells and the growth-inhibitory effects of OT suggest a potential use of oxytocin analogues for breast cancer treatment. Whereas no mutations of the oxytocin or V1a or V1b receptors have been found, over 60 different genetic mutations of the (renal) V2 receptor have been described which represent the cause for congenital nephrogenic diabetes insipidus.
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PMID:Vasopressin and oxytocin receptors. 873 52

Arginine vasopressin is the main hormone involved in the regulation of body fluid osmolality. The hormone is released by the posterior pituitary whenever water deprivation causes an increased plasma osmolality or whenever the cardiovascular system is challenged by hypovolaemia and/or hypotension. The main site of action of this hormone is the renal collecting duct, but vasopressin is also a potent vasopressor and neurotransmitter, it has a role in the secretion of corticotrophin, in the regulation of the cardiovascular system, temperature and other visceral functions. Vasopressin also promotes the release of coagulation factors by vascular endothelium and increases platelet aggregability. In addition to its classical contractile effect on uterine myometrial and mammary glandular myoepithelial cells, oxytocin acts as neurotransmitter, stimulates endometrial prostaglandin production, pituitary prolactin secretion, luteolysis, sperm transport and natriuresis, and may play a role in immune function. Sensorial stimuli arising from the cervix and vagina as well as stimulation of the breast can induce secretion of oxytocin from the posterior pituitary. There are many vasopressin and oxytocin analogues (agonists and antagonists) that are synthetized with the goal of increasing duration of action and selectivity for the receptor subtypes, while non-peptide antagonists are orally active. The oxytocin and the vasopressin V1a, V1b and V2 receptors have recently been cloned and shown to form a sub-family within the large superfamily of G-protein-linked receptors. Renal V2 receptors mediate vasopressin-induced water reabsorption via induction of intracellular cAMP production in collecting duct cells. Most remaining actions of vasopressin on blood vessel constriction, liver glycogenolysis, platelet adhesion, adrenal angiotensin II secretion and certain brain functions are mediated via V1a-type receptors that are coupled to a Gq/11 protein. V1 receptor activation leads to stimulation of phospholipases C, D and A2, and an increase in intracellular calcium. Vasopressin stimulates pituitary corticotrophin release via a third vasopressin receptor type (V1b) which is present in corticotrophs. Oxytocin induces myometrial contraction, endometrial prostaglandin F2a production, mammary gland milk ejection, renal natriuresis and specific sexual, affilitative and maternal behaviours via oxytocin receptors which are also coupled to a G1/11 protein. Although only one oxytocin receptor type has been cloned so far, recent binding studies indicate that uterine endometrial oxytocin receptors may constitute a distinct receptor subtype. Expression of oxytocin receptors have relevant up- and down-regulation by oestrogens and progesterone.
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PMID:[Hormones of the posterior region of the hypophyseal gland]. 986 66

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

Oxytocin is known to have an antidiuretic effect, but the mechanisms underlying this effect are not completely understood. We infused oxytocin by osmotic minipump into vasopressin-deficient Brattleboro rats for five days and observed marked antidiuresis, increased urine osmolality, and increased solute-free water reabsorption. Administration of oxytocin also significantly increased the protein levels of aquaporin-2 (AQP2), phosphorylated AQP2 (p-AQP2), and AQP3 in the inner medulla and in the outer medulla plus cortex. Immunohistochemistry demonstrated increased AQP2 and p-AQP2 expression and trafficking to the apical plasma membrane of principal cells in the collecting duct, and increased AQP3 expression in the basolateral membrane. These oxytocin-induced effects were blocked by treatment with the vasopressin V2 receptor antagonist SR121463B, but not by treatment with the oxytocin receptor antagonist GW796679X. We conclude that vasopressin V2 receptors mediate the antidiuretic effects of oxytocin, including increased expression and apical trafficking of AQP2, p-AQP2, and increased AQP3 protein expression.
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PMID:Molecular mechanisms of antidiuretic effect of oxytocin. 1821 7