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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration (ip) into fed mice of glucagon, epinephrine, vasopressin, oxytocin, angiotensin II, and dibutyryl cyclic AMP (dbcAMP) resulted in a rapid (within 2.5 to 15 min) elevation of PRPP content (two- to threefold) and in acceleration of the rate of de novo purine synthesis (twofold). Inhibition of the epinephrine-stimulated glycogenolysis by 2,5-anhydromannitol diminished markedly the acceleration effect of the hormone on the rate of purine synthesis. Administration of the hormones caused a rapid rise in the liver content of glucose 6-phosphate (G6P) by 15-70% but did not increase the ribose 5-phosphate (R5P) content. Liver ATP content was not affected. The hormones did not cause direct activation of PRPP synthetase, as gauged by the specific activity of the enzyme, its Km for substrates R5P and ATP, and its sensitivity to inhibition by ADP and GDP. The hormones did not increase the liver content of the enzyme activators Pi and Mg2+. The results suggest that the glycogenolytic hormones accelerate purine synthesis by a metabolic mechanism associated with the enhancement of glycogenolysis. PRPP synthesis is probably enhanced by the glycogenolysis-induced alterations in the cellular content of some metabolites other than R5P.
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PMID:Acceleration of purine synthesis in mouse liver by glycogenolytic hormones. 172 6

The effects of arginine-vasotocin and nucleotides on the steady-state kinetics of the adenylate cyclase activity in the epithelial cell membranes of the bullfrog (Rana catesbiana) bladder were studied. Arginine-vasotocin stimulated adenylate cyclase more effectively than oxytocin or arginine-vasopressin, with respect to both the maximal hormonal activation ratio relative to basal, and the hormone concentration yielding a half-maximal response (apparent Km). Arginine-vasotocin, GTP and its analogue guanyl-5'-yl imidodiphosphate (Gpp(NH)p) increased the Vmax of the basal adenylate cyclase activity, but showed no effect of the apparent Km of the system for ATP. In addition, Gpp(NH)p enhanced the arginine-vasotocin-stimulated adenylate cyclase activity, further increasing the Vmax, while GTP showed no statistically significant effect. Dual effects of GDP were apparent: it was stimulatory at 1 x 10(-5) mol/l and inhibitory at 1 x 10(-3) mol/l, on both the basal and the arginine-vasotocin-stimulated adenylate cyclase activity. Guanosine 5'-monophosphate, CTP, UTP and ITP showed no apparent effect on the enzyme activity. Sodium fluoride acted in the same manner as GTP on the adenylate cyclase system, increasing only basal activity. Adenylate cyclase activities exhibited pH optima that were less distinct in the presence than in the absence of Gpp(NH)p. The Arrhenius plot of the temperature experiment showed that a high-energy step was involved for activation by Gpp(NH)p or arginine-vasotocin. When the relative activation ratios by arginine-vasotocin at different ATP concentrations were studied, a distinct activation optimum was shown at 2.5 x 10(-4) mol ATP/l, either in the absence or presence of Gpp(NH)p. The possibility that GTP, GDP nd ATP play a regulatory role in the epithelial cells of the bullfrog bladder by adjusting the responsiveness of the system to a natural hormone, arginine-vasotocin, is discussed.
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PMID:Stimulatory and inhibitory effects of guanine nucleotides on arginine-vasotocin-sensitive adenylate cyclase in the epithelial cell membranes of the bullfrog bladder. 660 97

1. Oxytocin is known to act on autoreceptors of oxytocin neurones in the supraoptic nucleus (SON). We investigated whether oxytocin modulates putative oxytocin neurones by suppressing the GABAA receptor-mediated synaptic inputs on these cells. 2. GABAergic inhibitory postsynaptic currents (IPSCs) were recorded from SON neurones in hypothalamic slices from young rats. Oxytocin specifically reduced the amplitude of both spontaneous and evoked IPSCs, without altering their current kinetics. 3. The effect of oxytocin was observed in 70% of the magnocellular neurones recorded from the dorsomedial part of the SON. d(CH2)5OVT, a specific antagonist of oxytocin receptors, blocked the effect of oxytocin on the IPSCs. Vasopressin had no effect on oxytocin-sensitive SON neurones. 4. The intervals between spontaneous IPSCs were not affected by oxytocin. This suggested that oxytocin had a postsynaptic effect on SON neurones. 5. This postsynaptic origin was further substantiated by application of TTX, which blocked all evoked release but did not prevent the suppressive effect of oxytocin on the amplitude of the spontaneous IPSCs still present in the recording. The selective effect of oxytocin on IPSC amplitude was also maintained in nominally zero extracellular calcium. 6. Intracellular perfusion of SON neurones with GTP gamma S mimicked the effect of oxytocin on IPSCs, while GDP beta S, similarly applied, abolished the effect of oxytocin. 7. Application of calcium mobilizers such as thapsigargin and caffeine also reduced the amplitude of spontaneous IPSCs without significantly altering the frequency at which IPSCs occurred. 8. Thus, oxytocin depresses GABAergic synapses in the SON via modulation of the postsynaptic GABAA receptors. This would lead to disinhibition of SON neurones sensitive to oxytocin and could, therefore, be a powerful means of controlling the firing of oxytocin neurones.
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PMID:Postsynaptic mechanism of depression of GABAergic synapses by oxytocin in the supraoptic nucleus of immature rat. 896 Nov 90

Although the oxytocin receptor modulates intracellular Ca2+ ion levels in myometrium, the identities of signal molecules have not been clearly clarified. Our previous studies on oxytocin receptor signalling demonstrated that 80 kDa Ghalpha is a signal mediator [Baek, Kwon, Lee, Kim, Muralidhar and Im (1996) Biochem. J. 315, 739-744]. To elucidate the effector in the oxytocin receptor signalling pathway, we evaluated the oxytocin-mediated activation of phospholipase C (PLC) by using solubilized membranes from human myometrium and a three-component preparation containing the oxytocin receptor-Ghalpha-PLC-delta1 complex. PLC-delta1 activity in the three-component preparation, as well as PLC activity in solubilized membranes, was increased by oxytocin in the presence of Ca2+ and activated Ghalpha (GTP-bound Ghalpha). Furthermore the stimulated PLC-delta1 activity resulting from activation of Ghalpha via the oxytocin receptor was significantly attenuated by the selective oxytocin antagonist desGly-NH2d(CH2)5[Tyr(Me)2,Thr4]ornithine vasotocin or GDP. Consistent with these observations, co-immunoprecipitation and co-immunoadsorption of PLC-delta1 in the three-component preparation by anti-Gh7alpha antibody resulted in the PLC-delta1 being tightly coupled to activated Ghalpha on stimulation of the oxytocin receptor. These results indicate that PLC-delta1 is the effector for Ghalpha-mediated oxytocin receptor signalling.
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PMID:Phospholipase C-delta1 and oxytocin receptor signalling: evidence of its role as an effector. 951 91

Vasopressin-immunoreactive fibers have been visualized in the area of spinal lateral horn cells, including spinal sympathetic preganglionic neurons. The presence and nature of vasopressin receptors on neurons in this area were addressed using whole-cell patch-clamp techniques in transverse spinal cord slice preparations from neonatal rat. Bath applications of Arg8-vasopressin (VP) induced a slow-onset membrane depolarization accompanied by spike discharges and membrane oscillations. In voltage-clamp, applications of VP induced a reversible, tetrodotoxin-resistant and dose-dependent inward current in 90% of tested cells. This effect was blocked by a V1 receptor antagonist [D-(CH2)5 Tyr (Me)-VP], whereas a V2 receptor agonist [desamino-(D-Arg8)-vasopressin] was ineffective. Furthermore the applications of oxytocin produced significantly smaller depolarizations when compared with VP suggesting that, at least in the neonatal lateral horn cells, vasopressin rather than oxytocin is more effective ligand. Both the amplitude and duration of the VP effect were enhanced after intracellular dialysis with GTP-gamma-S, a non-hydrolyzable GTP analogue, whereas the inward current was significantly reduced after intracellular dialysis with GDP-beta-S, a stable analogue of GDP that competitively inhibits G-proteins. The observation that the VP-induced net inward current reversed at a potential close to the equilibrium for potassium ions and was associated with a decrease in membrane conductance in a majority of tested cells suggest mediation through closure of a leak potassium conductance. These data indicate that SPNs and other lateral horn cells possess functional G-protein-coupled V1-type vasopressin receptors that, in adult spinal cord, may contribute to CNS regulation of autonomic nervous system function.
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PMID:Vasopressin acting at V1-type receptors produces membrane depolarization in neonatal rat spinal lateral column neurons. 1007 94

Histaminergic neurons of the tuberomammillary nucleus (TM) project monosynaptically to the supraoptic nucleus (SON). This projection remains intact in our hypothalamic slices and permits investigation of both brief synaptic responses and the effects of repetitively activating this pathway. SON oxytocin (OX) neurons respond to single TM stimuli with fast IPSPs, whose kinetics resemble those of GABA(A) or glycine receptors. IPSPs were blocked by the Cl(-) channel blocker picrotoxin, but not by bicuculline or strychnine, and by histamine H(2), but not by H(1) or H(3) receptor antagonists, suggesting the presence of an ionotropic histamine receptor and the possible nonspecificity of currently used H(2) antagonists. G-protein mediation of the IPSPs was ruled out using guanosine 5'-O-(2-thiodiphosphate) (GDP-betaS), pertussis toxin, and Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPs), none of which blocked evoked IPSPs. We also investigated the effects of synaptically released histamine on dye coupling and neuronal excitability. One hundred seventy-three OX neurons were Lucifer yellow-injected in horizontal slices. Repetitive TM stimulation (10 Hz, 5-10 min) reduced coupling, an effect blocked by H(2), but not by H(1) or H(3), receptor antagonists. Because H(2) receptors are linked to activation of adenylyl cyclase, TM-stimulated reduction in coupling was blocked by GDP-betaS, pertussis toxin, and Rp-cAMPs and was mimicked by 8-bromo-cAMP, 3-isobutyl-1-methylxanthine, and Sp-cAMP. Membrane potentials of OX and vasopressin neurons were hyperpolarized, accompanied by decreased conductances, in response to bath application of 8-bromo-cAMP but not the membrane-impermeable cAMP. These results suggest that synaptically released histamine, in addition to evoking fast IPSPs in OX cells, mediates a prolonged decrease in excitability and uncoupling of the neurons.
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PMID:Ionotropic histamine receptors and H2 receptors modulate supraoptic oxytocin neuronal excitability and dye coupling. 1131 81

Glucocorticoid negative feedback in the brain controls stress, feeding, and neural-immune interactions by regulating the hypothalamic-pituitary-adrenal axis, but the mechanisms of inhibition of hypothalamic neurosecretory cells have never been elucidated. Using whole-cell patch-clamp recordings in an acute hypothalamic slice preparation, we demonstrate a rapid suppression of excitatory glutamatergic synaptic inputs to parvocellular neurosecretory neurons of the hypothalamic paraventricular nucleus (PVN) by the glucocorticoids dexamethasone and corticosterone. The effect was maintained with dexamethasone conjugated to bovine serum albumin and was not seen with direct intracellular glucocorticoid perfusion via the patch pipette, suggesting actions at a membrane receptor. The presynaptic inhibition of glutamate release by glucocorticoids was blocked by postsynaptic inhibition of G-protein activity with intracellular GDP-beta-S application, implicating a postsynaptic G-protein-coupled receptor and the release of a retrograde messenger. The glucocorticoid effect was not blocked by the nitric oxide synthesis antagonist N(G)-nitro-L-arginine methyl ester hydrochloride or by hemoglobin but was blocked completely by the CB1 cannabinoid receptor antagonists AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] and AM281 [1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide] and mimicked and occluded by the cannabinoid receptor agonist WIN55,212-2 [(beta)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate], indicating that it was mediated by retrograde endocannabinoid release. Several peptidergic subtypes of parvocellular neuron, identified by single-cell reverse transcripton-PCR analysis, were subject to rapid inhibitory glucocorticoid regulation, including corticotropin-releasing hormone-, thyrotropin-releasing hormone-, vasopressin-, and oxytocin-expressing neurons. Therefore, our findings reveal a mechanism of rapid glucocorticoid feedback inhibition of hypothalamic hormone secretion via endocannabinoid release in the PVN and provide a link between the actions of glucocorticoids and cannabinoids in the hypothalamus that regulate stress and energy homeostasis.
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PMID:Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. 1283 7

Supraoptic nucleus (SON) neurons secrete oxytocin or vasopressin in response to various physiological stimuli (e.g., lactation/suckling, dehydration). Released near fenestrated capillaries of the neurohypophysis, these peptides enter the blood and travel to peripheral target organs. The pervasive neuromodulator adenosine, acting at A1 receptors, is an important inhibitory regulator of magnocellular neuroendocrine cell activity. Another high-affinity adenosine receptor exists in this system, however. We examined the physiological effects of adenosine A2A receptor activation and determined its localization among various cell types within the SON. In whole cell patch-clamp recordings from rat brain slices, application of the selective adenosine A2A receptor agonist CGS-21680 caused membrane depolarizations in SON neurons, often leading to increased firing activity. Membrane potential changes were persistent (>10 min) and could be blocked by the selective A2A receptor antagonist ZM-241385, or GDP-beta-S, the latter suggesting postsynaptic sites of action. However, +/--alpha-methyl-(4-carboxyphenyl)glycine or TTX also blocked CGS-21680 effects, indicating secondary actions on postsynaptic neurons. In voltage-clamp mode, application of CGS-21680 caused a slight increase (approximately 8%) in high-frequency clusters of excitatory postsynaptic currents. With the use of specific antibodies, adenosine A2A receptors were immunocytochemically localized to both the magnocellular neurons and astrocytes of the SON. Ecto-5'nucleotidase, an enzyme involved in the metabolism of ATP to adenosine, was also localized to astrocytes of the SON. These results demonstrate that adenosine acting at A2A receptors can enhance the excitability of SON neurons and modulate transmitter release from glutamatergic afferents projecting to the nucleus. We suggest that adenosine A2A receptors may function in neuroendocrine regulation through both direct neuronal mechanisms and via actions involving glia.
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PMID:Activation of adenosine A2A receptors alters postsynaptic currents and depolarizes neurons of the supraoptic nucleus. 1664 7

Pulsatile neuropeptide secretion is associated with burst firing patterns; however, intracellular signaling cascades leading to bursts remain unclear. We explored mechanisms underlying burst firing in oxytocin (OT) neurons in the supraoptic nucleus in brain slices from lactating rats. Application of 10 pm OT for 30 min or progressively rising OT concentrations from 1 to 100 pm induced burst firing in OT neurons in patch-clamp recordings. Burst generation was blocked by OT antagonist and ionotropic glutamate receptor blockers or tetanus toxin. Blocking G-protein activation with suramin or intracellular GDP-beta-S, but not intracellularly administered antibody against the OT-receptor (OTR) C terminus, blocked bursts. Moreover, pretreatment of slices with pertussis toxin, an inhibitor of G(i/o)-proteins, did not block OT-evoked bursts, suggesting that G(i)/G(o) activation is unnecessary for burst generation. Thus, we further examined G alpha(q/11)-associated signaling pathways in OT-evoked bursts. Inhibition of phospholipase C or RhoA/Rho kinase did not block bursts. Activation of G betagamma subunits using myristoylated G betagamma-binding peptide (mSIRK) caused bursts, whereas intracellularly loaded antibody against G beta subunit blocked OT-evoked bursts. Blocking Src family kinase, but not phosphatidylinositol 3-kinase, occluded OT-evoked bursts. Similar to the effects of OT on EPSCs, mSIRK inhibited tonic EPSCs and elicited EPSC clustering. Finally, suckling caused dissociation of OTRs and G beta subunits from G alpha(q/11) subunits shown by coimmunoprecipitation and immunocytochemistry, supporting crucial roles for OTRs and G betagamma subunits in the milk-ejection reflex. We conclude that G betagamma subunits play a dominant role in burst firing evoked by applied OT or by suckling.
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PMID:Dominant role of betagamma subunits of G-proteins in oxytocin-evoked burst firing. 1731 86

The dimeric Gh protein is comprised of alpha (tissue transglutaminase) and beta (Calreticulin) subunits and known to be associated with FSH-, oxytocin-, or epinephrine-receptors/functions in their respective target cells. After establishing the FSH-induced activation of G alpha h/phospholipase C (PLC)-delta 1 pathway in rat Sertoli cells (SCs), we have attempted to identify a possible G alpha h-coupled novel FSH receptor (FSH-R). Remarkably, a protein with approximately 240-kDa molecular mass was coimmunoprecipitated with G alpha h in the fractionated membrane proteins of rat SCs. The protein was identified as myosin heavy polypeptide 9 (MyH9) by mass spectrometric analysis and immunoblotting. In addition, immunoprecipitation analysis reveals that MyH9 is constitutively associated with classical Gs-coupled FSH-R and inactive GDP-bound G alpha h at resting state of rat SCs, but did not interact with FSH directly as judged by Far-Western analysis. Upon the stimulation of higher levels of extracellular FSH (>1000 IU/liter), classical FSH-R induces the phosphorylation of MyH9, the dissociation of active GTP-bound G alpha h from FSH-R:MyH9 complexes, and the elicitation of G alpha h/PLC-delta 1 pathway-dependent Ca(2+)-influx in rat SCs. Furthermore, the specific inhibition of MyH9 ATPase activity with Blebbistatin dose-dependently suppressed FSH-induced G alpha h/PLC-delta 1 signaling and Ca(2+)-influx, but not intracellular cAMP accumulation in rat SCs, implying that MyH9 mediates FSH-induced activation of G alpha h/PLC-delta 1/IP(3)/Ca(2+)-influx pathway in rat SCs. This is the first to demonstrate that the filament protein MyH9 constitutively forms a ternary complex with FSH-R and inactive GDP-bound G alpha h. At higher FSH levels, this ternary complex executes an alternative signaling of classical Gs-coupled FSH-R through activating a Gs/cAMP-independent, G alpha h/PLC-delta 1 pathway in rat SCs.
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PMID:Nonmuscle myosin IIA (myosin heavy polypeptide 9): a novel class of signal transducer mediating the activation of G alpha h/phospholipase C-delta 1 pathway. 2006 7


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