Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using in situ hybridization methods that discriminate mRNAs encoding rat vasopressin V1a, V1b, V2 and oxytocin receptors in hepatic, brain and renal tissues, experiments were done to determine whether estrogen and/or progesterone influence renal vasopressin receptor (VR) or oxytocin receptor (OTR) transcripts. Estrogen induced OTR gene expression in the outer stripe of the outer medulla and increased expression of OTRs in macula densa cells. Outer stripe OTR mRNA peaked with 4 days of estrogen treatment, and decreased to undetectable levels with 31 days of treatment of ovariectomized females. Estradiol's induction of outer stripe OTR mRNA expression was blocked by the antiestrogen, tamoxifen, but was not affected by high levels of circulating oxytocin. A role for OTRs in regulating renal function independently of adrenal steroids was suggested by findings that adrenalectomized males showed high levels of OTR transcripts in outer stripe proximal tubule and cortical macula densa cells after 5 and 10 micrograms/100g of estradiol. Consistent with specialized roles for OTRs during female reproduction, OTR transcripts could not be detected in renal tissues of peri-parturient females, at times when OTR mRNA levels were very high in uterus. OTR gene expression in macula densa cells reappeared 4-8 days into lactation and attained control levels by day 20. Physiological experiments showed that estrogen + oxytocin decreased plasma [Na+] levels in ovariectomized rats at a time when proximal tubule OTR expression is maximal. These data are consistent with 1) cell-specific regulation by estrogen of renal OTR gene expression and 2) the possibility that OTRs may be important mediators of steroid-induced alterations in renal fluid and/or solute reabsorption.
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PMID:Oxytocin receptor gene expression in female rat kidney. The effect of estrogen. 871 83

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

Rats pretreated with an intracerebroventricular (i.c.v.) injection of 10 pmol of vasopressin or vasopressin analogs, including deamino-D-vasopressin, [pGlu4,Cyt6]vasopressin, [pGlu-Asn-Cys(Cys)]Pro-Leu-Gly-NH2, des-Gly-NH9(2)-vasopressin, Pro-Leu-Gly-NH2, Pro-Arg-Gly-NH2, became markedly hyper-responsive to the motor effects, 24 h later, to a subsequent challenge dose of vasopressin, but not vasopressin-related peptides. A vasopressin V1 receptor antagonist, [d(CH2)1(5),Tyr(Me)2]vasopressin, but not the vasopressin V2 receptor antagonist, [d(CH2)1(5),Tyr(Et)2,Val4]vasopressin, or a more selective vasopressin V2 receptor antagonist, [d(CH2)1(5),D-Ile2,Ile4]vasopressin, or the oxytocin receptor antagonist, [d(CH2)1(5),Tyr(Me)2,Thr4,Orn8,Tyr-NH9(2)]vasotocin ([d(CH2)1(5),Tyr(Me)2,Thr4,Tyr-NH9(2)]OVT), blocked vasopressin and vasopressin analog-induced sensitization. Furthermore, both vasopressin V2 receptor antagonists were found to sensitize the brain to a subsequent vasopressin injection. This vasopressin V2 receptor antagonist-induced sensitization was also blocked by the vasopressin V1 receptor antagonist. Next, we wanted to determine if this sensitization process could involve the release of endogenous vasopressin in the brain as reflected in an amplification of vasopressin mRNA expression. However pretreatment of rats with an i.c.v. vasopressin injection was not associated with an increase in vasopressin mRNA expression in the bed nucleus of the stria terminalis, medial amygdala or the paraventricular nucleus of the hypothalamus when measured 0, 1, 3, 7, 12, or 24 h after the first vasopressin injection. As many vasopressin analogs can induce sensitization, we suggest that a novel type of receptor may be involved in the sensitization process.
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PMID:Vasopressin-induced sensitization: involvement of neurohypophyseal peptide receptors. 878 13

Several studies indicate that oxytocin and vasopressin receptors in the human uterus are heterogeneous. We have investigated whether oxytocin and vasopressin bind to separate receptors in the day 21 and day 22 pregnant rat uterus and whether uterine vasopressin receptors are the same as the vascular V1A subtype. In isolated organ bath experiments we showed that the potency of d(CH2)5[Tyr(Me)2]vasopressin to inhibit vasopressin contraction in rat aorta was different from that in the day 21 pregnant uterus. Saturation curves of [3H]vasopressin in membranes from cultured aortic myocytes and pregnant uterus were linear and yielded the same 1 nM Kd values. However, the potency of d(CH2)5[Tyr(Me)2]vasopressin and of [Thr4,Gly7]oxytocin at antagonizing [3H]vasopressin confirmed the differences between the vascular smooth muscle and uterine vasopressin receptor. The peptides had respectively higher and lower affinity for aortic cell sites than for uterine sites. It was more difficult to distinguish pharmacological differences for oxytocin and vasopressin receptors in the uterus. On day 22, the high affinity of [Thr4,Gly7]oxytocin and oxytocin for both [3H]oxytocin and [3H]vasopressin binding sites was consistent with the notion that the uterus expresses essentially oxytocin receptors at this stage of gestation. However, oxytocin, vasopressin and three analogs showed a different potency for inhibiting [3H]oxytocin and [3H]vasopressin binding on day 21 versus day 22 of gestation. We conclude that in the rat uterus vasopressin binds to a receptor that is different from the vascular V1A subtype. Also, the binding sites for [3H]vasopressin and [3H]oxytocin on day 21 uterus membranes do not resemble the classical oxytocin receptor as described in the literature suggesting that on day 21 vasopressin and oxytocin bind in the uterus to a receptor that might be different from those currently characterized.
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PMID:Comparison of vasopressin and oxytocin receptors in the rat uterus and vascular tissue. 883 36

1. In a human vascular smooth muscle cell line (HVSMC), binding experiments with [3H]-arginine8-vasopressin (AVP) have shown the existence of a homogeneous population of binding sites with affinity (Kd value) of 0.65 nM and a maximum number of binding sites (Bmax) of 122 fmol mg-1 protein. 2. Nonlabelled compounds compete for [3H]-AVP binding in the HVSMC membrane with an order of potency of oxytocin > lyspressin > or = AVP > Thr4, Gly7-oxytocin > (beta-mercapto-beta-beta-cyclopentamethylenepropionyl-O-Me Tyr2, Arg8) vasopressin > desmopressin > OPC21268 > OPC31260. This order was markedly different from that observed in rat vascular smooth muscle cells (A10), a well-established V1A receptor system. 3. In HVSMC both oxytocin and AVP increased inositol 1,4,5-trisphosphate (IP3) production and [Ca2+]i response, but the efficacy of the responses was greater for oxytocin than AVP. 4. Reverse transcription-polymerase chain reaction (RT-PCR) assay detected only oxytocin receptor but not V1A or V2 receptors in HVSMC, whereas only V1A receptors were found in A10 cells. 5. In conclusion, in HVSMC only oxytocin receptors are expressed among the vasopressin receptor family, and they coupled to phosphatidyl inositol (PI) turnover/Ca2+ signalling. This unexpected observation should provide new insight into the functional role of the oxytocin receptor in a human vascular smooth muscle cell line.
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PMID:Oxytocin receptors expressed and coupled to Ca2+ signalling in a human vascular smooth muscle cell line. 885 93

The carboxyl terminus of the G protein alpha subunit is a key determinant of the fidelity of receptor activation. We have previously shown that the Gq alpha subunit (alpha q) can be made to respond to alpha i-coupled receptors by replacing its carboxyl terminus with the corresponding alpha i2, alpha o, alpha z residues. We now extend these findings in three ways: 1) carboxyl-terminal mutations of alpha q/alpha i chimeras show that the critical amino acids are in the -3 and -4 positions, 2) exchange of carboxyl termini between alpha q and alpha z allows activation by receptors appropriate to the carboxyl-terminal residues, and 3) we identify receptors that either do or do not activate the expected carboxyl-terminal chimeras (alpha q/alpha i, alpha q/alpha s, alpha s/alpha q). Replacement of the five carboxyl-terminal amino acids of alpha q with the alpha s sequence permitted an alpha s-coupled receptor (the V2 vasopressin receptor but not the beta 2-adrenergic receptor) to stimulate phospholipase C. Replacement of the five carboxyl-terminal amino acids of alpha z with residues of alpha q permitted certain alpha q-coupled receptors (bombesin and V1a vasopressin receptors but not the oxytocin receptor) to stimulate adenylyl cyclase. Thus, the relative importance of the G alpha carboxyl terminus in permitting coupling to a new receptor depends on the receptor with which it is paired. These studies refine our understanding and provide new tools with which to study the fidelity of receptor/G alpha activation.
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PMID:Carboxyl-terminal mutations of Gq alpha and Gs alpha that alter the fidelity of receptor activation. 886 34

We investigated the mechanisms that regulate the efficacy of agonists in the arginine-vasopressin (AVP)/oxytocin (OT) receptor system. In this paper, we present evidence that AVP, a full agonist of the vasopressin receptors, acts as a partial agonist on the oxytocin receptor. We also found that AVP becomes a full agonist when two aromatic residues of the oxytocin receptor are replaced by the residues present at equivalent positions in the vasopressin receptor subtypes. Our results indicate that these two residues modulate the response of the oxytocin receptor to the partial agonist AVP.
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PMID:Two aromatic residues regulate the response of the human oxytocin receptor to the partial agonist arginine vasopressin. 895 47

Comparative studies of monogamous and nonmonogamous voles demonstrate species differences in the regional expression of oxytocin (OT) receptors in the brain. These species differences have not been observed with other neurotransmitter receptors (except vasopressin). Species differences for OT receptor distribution were also observed in other microtine and murine species selected as monogamous or promiscuous. These chemical neuroanatomic differences appear to be functionally relevant, as treatments with selective OT agonists and antagonists influence those behaviors that appear critical to pair bonding in the monogamous prairie vole. To investigate the mechanism controlling tissue-specific expression of OT receptors, we sequenced the OT receptor gene in both prairie voles and montane voles. The findings are inconclusive. Although both species differ markedly from rat and human in their regulatory (but not their coding) sequences, the species show very subtle differences from each other. Ongoing studies are investigating the consequences of these subtle differences between prairie and montane voles. At the same time, several transactivating factors that might influence OT receptor expression need to be explored. NOTE ADDED IN PROOF: The rat oxytocin receptor gene sequence, cited in FIGURES 4 and 5, was based on an error published in ref. 22. The corrected sequence has now been published (Rosen et al. 1996. Proc. Natl. Acad. Sci USA 93: 12501). The correct sequence shows greater homology with the vole oxytocin receptor gene sequences, but the remaining differences support the argument made herein for species differences in regional receptor expression.
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PMID:Molecular aspects of monogamy. 907 59

The effect of three oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin was investigated in conscious male rats infused with hypotonic saline. Infusion of oxytocin at 100 pg/min produced plasma concentrations of 12.7 +/- 3.3 pmol/l and led to significant increases in sodium excretion, urine flow and glomerular filtration rate (GFR). The increase in sodium excretion of 42 +/- 9% during oxytocin infusion was significantly decreased by all three antagonists to 15 +/- 5% (10 ng [mercapto-proprionic acid1, D-Tyr(Et)2,Thr4,Orn8]-oxytocin/min), 13 +/- 5% (5 ng desGly9[D-Trp2,Thr4,Orn8]-dC6oxytocin/min) and 4 +/- 5% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/min). Similarly, the increase in urine production of 22 +/- 5% associated with oxytocin infusion was significantly decreased to 4 +/- 3% (5 ng desGly9[D-Trp2,D-Thr4,Orn8]-dC6 oxytocin/min) and 1 +/- 4% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/ min). All three antagonists blocked the oxytocin-induced increase in GFR when infused at 10 ng/min. Infusion of vasopressin at 160 pg/min produced plasma concentrations of 10.1 +/- 2.1 pmol/l and this led to a significant increase in sodium excretion and a significant decrease in urine flow rate. None of the antagonists had any effect on the natriuretic or antidiuretic actions of vasopressin suggesting that different receptors are involved in these renal actions of the two peptides.
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PMID:Effect of oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin in the rat. 907 83

Gonadotropes synthesize and secrete LH and FSH under the control of GnRH, which acts via phosphoinositidase C (PIC)-linked G protein coupled receptors. Additionally, gonadotropin released from the pituitary is influenced by oxytocin, a peptide that has been shown to play a role in generation of the preovulatory LH surge. Although oxytocin receptors are present in the pituitary, studies have identified their presence on lactotropes but not on gonadotropes, raising the question of which cells act as the direct target of oxytocin in gonadotrope regulation. In this study, we examined effects of oxytocin on alphaT3-1 cells, a gonadotrope-derived cell line. Oxytocin, vasopressin, and vasotocin each stimulated accumulation of [3H]inositol phosphates in cells prelabeled with [3H]inositol, indicating activation of PIC. The rank order of potency (oxytocin > vasotocin > vasopressin) and sensitivity to inhibition by oxytocin and vasopressin receptor antagonists, revealed the effect to be mediated by oxytocin-selective receptors. Like other PIC activators, these nonapeptides caused biphasic (spike-plateau) increases in the cytosolic Ca2+. The spike response to oxytocin and GnRH were both retained in Ca2+-free medium, reflecting mobilization of intracellular Ca2+, and were comparably reduced by thapsigargin, implying mobilization of Ca2+ from a shared thapsigargin-sensitive intracellular pool. Brief stimulation with oxytocin, vasopressin, or vasotocin prevented subsequent Ca2+ responses to oxytocin, but not to GnRH, suggesting that the oxytocin receptor undergoes rapid homologous desensitization and reinforcing the interpretation that the nonapeptides act via the same receptor type. Oxytocin did not increase Ca2+ in cells stimulated with GnRH, whereas GnRH caused a spike Ca2+ increase even in the presence of oxytocin, implying that different mechanisms of desensitization (Ca2+ pool depletion and receptor uncoupling) are operating for two distinct PIC-coupled receptors in these cells. The demonstration that oxytocin acts directly via PIC-linked, oxytocin-selective receptors to increase cytosolic Ca2+ in a gonadotrope-derived cell line is consistent with the possibility that oxytocin has a comparable effect on nonimmortalized gonadotropes.
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PMID:Oxytocin receptor-mediated activation of phosphoinositidase C and elevation of cytosolic calcium in the gonadotrope-derived alphaT3-1 cell line. 911 4


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