Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Available data concerning the effect of oxytocin on memory are often inconsistent. In the present study it was found that oxytocin, intracerebroventricularly injected to adult male rats in a dose range of 1 fg-10 ng/rat immediately after a 5-minute encounter with a juvenile, significantly reduces the social investigation time of the adult rat towards the same juvenile during a second encounter (120 min later) with two peaks of activity, at 10 fg and 1 ng/rat. Larger doses of oxytocin were ineffective. The oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin, injected 5 min before oxytocin by the same route and at the same doses, while being ineffective per se, completely abolished the memory-improving effect of a low dose of oxytocin (1 ng/rat) and, on the other hand, turned into memory-improving the effect of a high dose of oxytocin (500 ng/rat).
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PMID:Polymodal dose-response curve for oxytocin in the social recognition test. 759 90

The effect of NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine, two inhibitors of nitric oxide synthase, on apomorphine- and oxytocin-induced penile erection and yawning, was studied in male rats after intravenous and intracerebroventricular administration. Both compounds prevented dose-dependently apomorphine and oxytocin responses, when given systemically (5-50 mg/kg) or centrally (30-500 micrograms per rat), but NG-nitro-L-arginine methyl ester was about 5 times more potent than NG-monomethyl-L-arginine. The D-isomer of NG-monomethyl-L-arginine, which does not inhibit nitric oxide synthase, was ineffective. The results suggest that central nitric oxide is involved in the expression of penile erection and yawning induced by apomorphine and oxytocin.
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PMID:Nitric oxide synthase inhibitors prevent apomorphine- and oxytocin-induced penile erection and yawning in male rats. 768 37

We studied the capacity of different GH preparations, natural human (h)GH, recombinant hGH (rhGH), rat (r)GH, ovine (o)GH, bovine (b)GH and porcine (p)GH, and ovine prolactin (oPRL), to stimulate lactogenesis in ovario-hysterectomized pregnant rats or intact lactating rats treated with bromocriptine (BC). Ovariohysterectomy (OVX-HYS) performed at 0800 h on day 19 of pregnancy induced lactogenesis, i.e. increases in mammary casein and lactose and positive response to the oxytocin test, 28 h later. Lactogenesis was prevented by treatment with BC (1.5 mg/kg) immediately after surgery (OVX-HYS-BC). The hormones were given at doses of 0.25 or 0.5 mg/rat (except rhGH given only at 0.5 mg/rat) at 1200 and 2000 h on day 19. Casein was increased by both doses of oPRL and hGH, rhGH and 0.25 mg oGH, and lactose by both doses of oPRL, rhGH and 0.25 mg rGH. The other GH preparations had no effect. The oxytocin test demonstrated the presence of milk in the mammary tissues of the OVX-HYS rats and in the OVX-HYS-BC plus oPRL (0.25 and 0.5 mg) or rhGH-treated groups. Injection of BC to pregnant rats at 2000 h on day 20 and at 0800 h on day 21 decreased litter growth on the first 4 days postpartum. Two-thirds of the litters resumed growth after day 4, indicating the recuperation of milk production, while the rest never recuperated. Serum prolactin in BC-treated rats was reduced until day 4 postpartum. On day 6 the rats which had recuperated had normal values, while those which had still not recuperated had lower values. BC-treated rats were injected s.c. with 0.25 mg each of oPRL, hGH, rGH, oGH, bGH or pGH, or 0.25 or 0.5 mg rhGH/rat, immediately postpartum and 12, 24 and 36 h later. hGH and 0.5 mg rhGH induced levels of milk production similar to controls except on day 3. oPRL and rhGH (0.25 mg), induced a partial reversion of the effect of BC. rGH and oGH had a slight effect on days 1 and 2 and all the litters resumed growth on day 7. In contrast, pGH and bGH were inactive. The affinity of hGH for the prolactin receptor, measured as displacement of 125I-labelled oPRL binding to crude liver membranes, was comparable with that of oPRL. While rhGH was ten times less active than oPRL, rPRL was 100 times lower and all the other GH preparations had at least 10(4) times lower capacity to displace 125I-labelled oPRL.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lactogenic actions of different growth hormone preparations in pregnant and lactating rats. 796 4

Modifications to the previously reported spiroindenylpiperidine camphor-sulfonamide oxytocin (OT) antagonist L-366,509 have produced a new series of o-tolylpiperazine (TP) camphor-sulfonamides. A number of analogues in the TP series that incorporate a modified or unmodified L-methionine sulfone amide at the C2 endo position on the camphor ring exhibit high affinity for OT receptors (IC50 = 1.3-15 nM) and good selectivity for binding to OT versus arginine vasopressin V1a and V2 receptors. Several of these analogues were additionally characterized as potent antagonists of OT-stimulated contractions of the isolated and/or in situ rat uterus. Compound 7 (L-368,899) exhibited the best overall profile of OT receptor affinity (IC50 = 8.9 nM, rat uterus; 26 nM, human uterus), potency for inhibition of OT-stimulated contractions of the isolated rat uterus (pA2 = 8.9) and in situ rat uterus (AD50 = 0.35 mg/kg after intravenous (i.v.) administration and 7.0 mg/kg after intraduodenal administration), aqueous solubility (3.7 mg/mL at pH 5.0), and oral bioavailability in several species (35% (rat), 25% (dog), and 21% (chimpanzee) as estimated from radioreceptor determination of drug levels in plasma after oral and i.v. dosing). On the basis of these favorable properties, 7 has begun clinical testing for use as an oral and i.v. tocolytic agent. Molecular modeling alignment studies have provided support for the hypothesis that the TP camphor-sulfonamide portion of the non-peptide structures may serve as a mimetic of the important D-AA2-Ile3 dipeptide (AA = aromatic amino acid) found in many potent OT antagonists from the cyclic hexapeptide and OT analogue structural classes.
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PMID:1-((7,7-Dimethyl-2(S)-(2(S)-amino-4-(methylsulfonyl)butyramido)bicyclo [2.2.1]-heptan-1(S)-yl)methyl)sulfonyl)-4-(2-methylphenyl)piperaz ine (L-368,899): an orally bioavailable, non-peptide oxytocin antagonist with potential utility for managing preterm labor. 812 95

Pharmacological properties of the anti-ulcer drug 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl] methyl]-amino-N-methylbenzamide (DQ-2511, CAS 104775-36-2) on the central and autonomic nervous systems, smooth muscle, gastrointestinal system, and other miscellaneous systems were investigated. 1. DQ-2511 showed little or no influence on general behavior, spontaneous motor activity, hexobarbital sleeping time (mouse), conditioned avoidance response (rat), body temperature (rabbit), EEG or spinal reflex (cat) after oral administration (300-1000 mg/kg) or intravenous injection (15, 50 mg/kg). It also had no anticonvulsant or analgesic activities (mouse). 2. DQ-2511 had no influence on pupil size (rabbit). It reduced or tended to reduce contractile responses of the nictitating membrane induced by electrical stimulation of pre- and post-ganglionic sympathetic nerve (cat) at the highest dose. The drug inhibited the pressor response to norepinephrine, but had little or no inhibitory effect on the depressor response to acetylcholine at the highest dose (dog). 3. DQ-2511 reduced contractile responses to nicotine, BaCl2, acetylcholine, histamine and serotonin (isolated guinea pig ileum), to acetylcholine and histamine (trachea), and to norepinephrine (vas deferens) at high concentrations. It also inhibited spontaneous and oxytocin-induced motility (isolated rat uterus). 4. DQ-2511 decreased gastric motility in a dose-related manner at intravenous doses of 5-50 mg/kg (dog). It also reduced gastric emptying rate at oral doses of 100-1000 mg/kg, and gastric secretion at intraperitoneal doses of 100-300 mg/kg (rat). On the other hand, it induced no definite changes in intestinal motility (dog) or gastrointestinal transit (mouse).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:General pharmacological profile of the new anti-ulcer drug 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl]-amino-N -methylbenzamide. 832 2

The posterior pituitary hormone, oxytocin (OT), has been shown to have either a stimulatory or an inhibitory effect on PRL secretion depending on the route of administration. Whether its central inhibitory effect involves the tuberoinfundibular dopaminergic (TIDA) neuron was the focus of this study. Adult female Sprague-Dawley rats ovariectomized for 1 week, implanted with sc estrogen-containing capsules and intracerebroventricular cannulas for 6 more days were used. TIDA neuron activity was determined by measuring the concentration of 3,4-dihydroxyphenylacetic acid or 3,4-dihydroxyphenylalanine in the median eminence by HPLC with electrochemical detection. Intracerebroventricular injection of OT induced both dose (0.01-1 microgram/rat)- and time (30-90 min)-dependent increases in 3,4-dihydroxyphenylalanine or 3,4-dihydroxyphenylacetic acid levels in the median eminence. Serum PRL levels were also decreased 30 min after the injection. The use of a specific OT antagonist, [d(CH2)5, Tyr(Me)2, Orn8]vasotocin, not only blocked the effect of OT on TIDA neuron activity, it further lowered it to below control levels, indicating the existence of an endogenous OT activity. When 1 microgram OT was administered at 1200 h, it also reversed the diurnal decrease in TIDA neuron activity at 1500 h. The effects of OT on the electrical activities of dorsomedial arcuate neurons were also tested using single unit recording in brain slices. In 33 neurons tested with OT, 66.7% were stimulated by OT in 0.5- to 50-nmol doses, and no inhibitory effect was observed. The rest were not responsive. In conclusion, both neurochemical and electrophysiological studies demonstrated that central OT may play a stimulatory role in regulating the TIDA neurons and, in turn, inhibition of PRL secretion.
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PMID:Stimulatory effect of central oxytocin on tuberoinfundibular dopaminergic neuron activity and inhibition on prolactin secretion: neurochemical and electrophysiological studies. 882 66

The alpha2-adrenergic agonist clonidine and the neuropeptide oxytocin, inhibit sodium intake when injected intracerebroventricularly (i.c.v.). The present work investigates whether (1) vasopressin also inhibits sodium intake when injected i.c.v., and (2) the effect of oxytocin and of vasopressin on sodium intake is affected by i.c.v. injection of idazoxan, an alpha2-adrenergic antagonist. Clonidine (30 nmol), oxytocin (40, 80 nmol) and vasopressin (40, 80 nmol) were injected i.c.v. 20 min prior to a 1.5% NaCl appetite test, in rats depleted of sodium for 24 h by a combination of a single s.c. injection of furosemide (10 mg/rat) and removal of ambient sodium. Every dose of clonidine, oxytocin and vasopressin inhibited the 1.5% NaCl intake. Seizures were observed with the higher dose of vasopressin, but not with either dose of oxytocin. The effect of i.c.v. injection of clonidine (30 nmol), oxytocin (80 nmol) or vasopressin (40 nmol) was partially inhibited by prior i.c.v. injection of idazoxan (160, 320 nmol). The results suggest that the inhibition of 1.5% NaCl intake induced by i.c.v. injection of neuropeptides in sodium-depleted rats depends, in part, on the activation of central alpha2-adrenoceptors.
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PMID:Idazoxan and the effect of intracerebroventricular oxytocin or vasopressin on sodium intake of sodium-depleted rats. 922 97

The previously reported oxytocin antagonist L-371,257 (2) has been modified at its acetylpiperidine terminus to incorporate various pyridine N-oxide groups. This modification has led to the identification of compounds with improved pharmacokinetics and excellent oral bioavailability. The pyridine N-oxide series is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1 nM, cloned human oxytocin receptor) and in vivo (intravenous AD50 = 0.71 mg/kg in the rat), excellent oral bioavailability (90% in the rat, 96% in the dog), good aqueous solubility (>8.5 mg/mL at pH 5.2) which should facilitate formulation for iv administration, and excellent selectivity against the human arginine vasopressin receptors. Incorporation of a 5-fluoro substituent on the central benzoyl ring of this class of oxytocin antagonists enhanced in vitro and in vivo potency but was detrimental to the pharmacokinetic profiles of these compounds. Although lipophilic substitution around the pyridine ring of compound 30 gave higher affinity in vitro, such substituents were a metabolic liability and caused shortfalls in vivo. Two approaches to prevent this metabolism, addition of a cyclic constraint and incorporation of trifluoromethyl groups, were examined. The former approach was ineffective because of metabolic hydroxylation on the constrained ring system, whereas the latter showed improvement in plasma pharmacokinetics in some cases.
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PMID:Development of orally active oxytocin antagonists: studies on 1-(1-[4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]-2- methoxybenzoyl]piperidin-4-yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and related pyridines. 962 56

Thymic epithelium, including nurse cells (TEC/TNC), as well as other thymic stromal cells (macrophages and dentritic cells), express a repertoire of polypeptide belonging to various neuroendocrine protein families (such as the neurophypophysial, tachykinin, neurotensin and insulin families). A hierarchy of dominance exists in the organization of the thymic repertoire of neuroendocrine precursors. Oxytocin (OT) is more expressed in the TEC/TNC than vasopressin (VP); insulin-like growth factor 2 (IGF-2) thymic expression predominates over IGF-1, and much more over (pro)insulin. Thus, OT was proposed to be the self antigen of the neurohypophysial family, and IGF-2 the self antigen precursor of the insulin family. The dual role of the thymus in T-cell life and death is recapitulated at the level of the thymic neuroendocrine protein repertoire. Indeed, thymic polypeptides behave as accessory signals involved in T-cell development and positive selection according to the cryptocrine model of signaling. Moreover, thymic neuroendocrine polypeptides are the source of self antigens presented by thymic MHC molecules to developing pre-T cells. This presentation might induce the negative selection of T cells bearing a randomly rearranged antigen receptor (TCR) oriented against neuroendocrine families. Using an animal model of autoimmune type 1 diabetes (BB rat), we have shown a defect in intrathymic expression of the self antigen of the insulin family (IGF-2) and in IGF-2-mediated T-cell education to recognize and tolerate the insulin family. Altogether these studies have enlightened the crucial role played by the thymus in the induction of the central self tolerance of neuroendocrine families. The tolerogenic properties of thymic self peptides could be used in a novel type of vaccination for the prevention of autoimmune diseases.
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PMID:The thymic repertoire of neuroendocrine-related self antigens: biological role in T-cell selection and pharmacological implications. 987 42

The product of the ob gene protein, leptin, has been suggested to function as an endogenous mediator of the cardiovascular system via sympathetic nerve activity. Moreover, extensive distribution of leptin receptor-like immunoreactivity has been demonstrated in the choroid plexus, cerebral cortex, hippocampus, thalamus and hypothalamus, especially in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In this study, we have investigated the in vivo effects of leptin on plasma arginine-vasopressin (AVP) secretion and the level of AVP messenger ribonucleotic acid (AVP mRNA) in the SON of conscious rats. Intracerebroventricularly administered leptin increased plasma AVP concentration in a dose-dependent manner (0-400 pmol/rat). The maximal effect was obtained at 15 min after the administration of leptin. Furthermore, in Northern blot analyses, the levels of AVP mRNa in the SON increased approximately 2-fold from the basal level after the administration of leptin. AVP mRNA expression in the PVN was also increased by leptin. However, leptin had no effects on plasma oxytocin (OXT) secretion and OXT gene expression in the SON. In conclusion, leptin is involved in AVP secretion via the central nervous system, however, its physiological role is unknown.
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PMID:Centrally administered murine leptin stimulates plasma arginine-vasopressin secretion and increases the level of mRNA expression in the supraoptic nucleus of conscious rats. 1051 84


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