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

It is now widely accepted that ATP functions as a signalling substance in the nervous system. The presence of P2 receptors mediating the action of extracellular ATP in brain regions involved in hormonal regulation raises the possibility that a similar role for ATP might also exist in the neuroendocrine system. In this study, the release from the rat isolated neurohypophysis preparation of endogenous ATP, oxytocin and vasopressin (AVP) were measured simultaneously using luciferin-luciferase and RIA techniques. After 70 min preperfusion, electrical field stimulation caused a rapid increase in the amount of ATP in the effluent and the release of AVP and oxytocin also increased stimulation-dependently. Inhibition of voltage-dependent Na+ channels by tetrodotoxin (1 microM) reduced the stimulation-evoked release of AVP and oxytocin; however, the evoked release of ATP remained unaffected. The effect of endogenous ATP on the hormone secretion was tested by suramin (300 microM), the P2 receptor antagonist. Suramin significantly increased the release of AVP, and the release of oxytocin was also enhanced. ATP, when applied to the superfusing medium, decreased the release of AVP, but not that of oxytocin, and its effect was prevented by suramin. ATP (60 nmol), added to the tissues, was readily decomposed to ADP, AMP and adenosine measured by HPLC combined with ultraviolet light detection, and the kinetic parameters of the enzymes responsible for inactivation of ATP (ectoATPase and ecto5'-nucleotidase) were also determined (Km=264+/-2.7 and 334+/-165 microM and vmax=6.7+/-1.1 and 2.54+/-0.24 nmol/min per preparation (n=3) for ectoATPase and ecto5'-nucleotidase respectively). Taken together, our data demonstrate the stimulation-dependent release, P2 receptor-mediated action and extracellular metabolism of endogenous ATP in the posterior lobe of the hypophysis and indicate its role, as a paracrine regulator, in the local control of hormone secretion.
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PMID:Local regulation of vasopressin and oxytocin secretion by extracellular ATP in the isolated posterior lobe of the rat hypophysis. 1007 81

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

Distal kidney cells (A6) from Xenopus laevis were cultured to confluency on porous supports. Tissues were mounted in Ussing-type chambers to measure short-circuit current (Isc), transepithelial conductance and capacitance, and to analyse the fluctuation in Isc. In the absence of apical NaCl, but with normal basolateral NaCl Ringer's solution, extracellular addition of ATP, oxytocin, a membrane-permeant cAMP derivative, and forskolin produced a transient increase of the electrical parameters. Noise analysis revealed a spontaneous Lorentzian component. All responses depend strictly on the presence of basolateral Cl- and are caused by the activation of an apical (CFTR type) Cl- permeability. Repetitive treatment with ATP (or oxytocin) resulted in refractoriness. ATP and oxytocin acted antagonistically, whereas cAMP and ATP had additive effects. Incubation with the vesicular Ca2+ pump inhibitor thapsigargin or application of the Ca2+ channel blocker nifedipine elicited finite but variable Cl- channel activity. After treatment with nifedipine or thapsigargin, the response to oxytocin was severely impaired. We speculate that not only cAMP but also cell Ca2+ plays a crucial role in the activation of CFTR in A6. Ca2+ may be multifunctional but the rise in capacitance (apical area) observed with all stimulants strongly suggests its involvement in, and contribution to, exocytosis in the process of the CFTR-mediated transcellular Cl- movements.
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PMID:Secretory apical Cl- channels in A6 cells: possible control by cell Ca2+ and cAMP. 1039 65

The work is devoted to the investigation of ethanol direct effect on the transmembrane Ca2+ metabolism in the intracellular structures of myometrium. In the experiments in vitro it has been shown that the Mg2+, ATP-dependent system for Ca2+ accumulation in endoplasmic reticulum is more sensitive then Ca(2+)-accumulating system in mitochondria. It has also been found that the oxytocin insensitive part of Mg2+, ATP-dependent Ca2+ accumulation of the endoplasmic reticulum is less resistant to ethanol inhibition than the oxytocin sensitive one. The data above revealed allow to discuss mechanism of ethanol action on the intracellular Ca2+ homeostasis in myometrium.
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PMID:[Effector action of ethanol on the accumulation of Ca2+ in intracellular structures of uterine smooth muscle]. 1079 Oct 72

Much is now known about the electrophysiological properties of the magnocellular neurones of the hypothalamus. Oxytocin neurones are characterized by an intermittent high frequency discharge during suckling that leads to the pulsatile release of oxytocin into the blood and to subsequent milk ejection. Vasopressin neurones are characterized by their asynchronous phasic activity (bursting) during maintained vasopressin release and the subsequent regulation of water balance. In both cases, it is the clustering of spikes, albeit with different time courses for each peptide, that facilitates hormone release. The mechanism underlying this differential facilitation is one of the major unanswered questions in neuroendocrinology. This paper considers recent evidence that indicates that ATP, co-secreted with vasopressin and oxytocin, may play a key role in the regulation of stimulus-secretion coupling in the neurohypophysis. The activity of the type (II) Ca2+-activated K+ (K(Ca)) channel found in the nerve terminals was significantly increased in the presence of ATP on the cytoplasmic side of the channel. Extracellular ATP, in contrast, inhibited the type II K(Ca) current in a dose-dependent manner. Thus, intracellular and extracellular ATP exert opposite effects on the type II K(Ca) channel of neurohypophysial terminals. Furthermore, ATP opens P2X2 channels to increase intracellular [Ca2+] in the nerve terminals and subsequent arginine vasopressin (AVP) release. In contrast, adenosine, acting via A1 receptors, specifically inhibits only the N-type Ca2+ channel, thus decreasing neuropeptide release. These multiple, conflicting effects of ATP and its metabolite adenosine could explain the patterns of AVP release observed during physiological stimulation in vivo.
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PMID:Excitatory versus inhibitory modulation by ATP of neurohypophysial terminal activity in the rat. 1079 8

In order of estimating some regularities of ethanol direct (effectory) effect to transmembrane calcium metabolism in the myometrium the action of this substance on the energy-dependent Ca(2+)-transporting systems of the uterine myocytes subcellular structures has been studied. The systems of Mg2+, ATP-dependent Ca2+ transport regarding their sensitivity to ethanol inhibitory effect were displayed as satisfying the following sequences: endoplasmic reticulum calcium pump > plasma membrane solubilized Ca2+, Mg2+, ATP-ase > mitochondrial Ca(2+)-accumulating system = plasma membrane calcium pump. Alongside with the latter, the oxytocin-insensitive component of Mg2+, ATP-dependent Ca2+ accumulation in the endoplasmic reticulum was defined to be less resistant to inhibitory effect of ethanol if compared with the oxytocin-sensitive one. On the base of the data received some mechanisms of ethanol effectory action on the intracellular calcium homeostasis in the myometrium cells are under the discussion.
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PMID:[Effect of ethanol on the activity of the energy-dependent Ca2+-transporting system of myometrial cells]. 1097 56

The A1 catecholamine neurons of the caudal ventrolateral medulla transmit hemodynamic information to the vasopressin (VP) neurons in the hypothalamus. These neurons corelease ATP with norepinephrine. Perifused explants of the hypothalamoneurohypophyseal system were used to investigate the role of these substances on VP release. ATP (100 micrometer) increased VP release 1.5-fold (p = 0.027). The response was rapid but unsustained. It was blocked by the P(2) receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). The alpha(1)-adrenergic agonist phenylephrine (PE; 100 micrometer) also increased VP release by 1.5-fold (p = 0.014). Again, the response was rapid and unsustained. However, simultaneous perifusion of explants with ATP (100 micrometer) and PE (100 micrometer) resulted in a threefold to fourfold increase in VP release, which was sustained for as long as 4 hr. There was a similar synergistic effect of ATP and PE on oxytocin release. Interestingly, the synergistic response was delayed approximately 40 min relative to the response to either agent alone. Several experiments were performed to elucidate the cellular mechanisms of this synergism. The effect was blocked by PPADS, a protein kinase C inhibitor (bisindolylmaleimide I HCl), and actinomycin, an inhibitor of gene transcription. These data suggest that P(2X) receptor activation, PKC-mediated phosphorylation, and gene transcription are required for the synergistic response. The marked synergism of these coreleased agents is probably important to achieve sustained increases in plasma VP in response to prolonged hypotension. These observations may also have broad applications to CNS function, because ATP may be coreleased at noradrenergic synapses throughout the CNS.
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PMID:Purinergic and adrenergic agonists synergize in stimulating vasopressin and oxytocin release. 1110 96

The supraoptic nuclei are innervated by the A1 neurons of the caudal ventrolateral medulla. Substances colocalized in the A1 terminals include norepinephrine (NE), substance P (SP), ATP, and neuropeptide Y (NPY). ATP, acting at P(2x) receptors, caused rapid and unsustained stimulation of vasopressin (VP) and oxytocin (OT) release from perifused explants of the hypothalamo-neurohypophysial system. SP elicited a concentration-dependent stimulation of VP and OT release that was large and sustained compared with other stimuli. ATP, but not phenylephrine (PE, alpha(1)-adrenergic agonist), augmented the response to SP (1 microM). In contrast, NPY did not alter basal nor ATP-induced VP or OT release, but it did cause sustained potentiation of PE-induced VP and OT release. The Y(1)-agonist, [Leu(31),Pro(34)]-NPY, increased VP and OT release, suggesting that the ineffectiveness of NPY reflects opposing actions at pre- and postsynaptic receptors. However, [Leu(31),Pro(34)]-NPY did not potentiate hormone responses to ATP or PE. The differential responses to these colocalized neurotransmitters and neuropeptides illustrate the range of potential responses that stimulation of this pathway might elicit from supraoptic neurons.
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PMID:Substance P and NPY differentially potentiate ATP and adrenergic stimulated vasopressin and oxytocin release. 1112 36

The effects of subacute, acute and chronic ethanol exposure on the activity of Ca(2+)-accumulating systems of mitochondria and endoplasmic reticulum in myometrial cells of nonpregnant estrogen-treated rats were studied. It has been shown that the activity of Ca(2+)-accumulating system of mitochondria was higher than the activity of Ca(2+)-accumulating system of endoplasmic reticulum in myometrial cells from control, acute and subacute treated with ethanol rats. Under ethanol chronical assumption both Ca(2+)-accumulation in mitochondria and Ca(2+)-transporting activity of endoplasmic reticulum are inhibited. In the latter ease Mg2+, ATP-dependent Ca(2+)-pump lost its sensitivity to oxytocin.
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PMID:[Accumulation of Ca ions in intracellular structures of rat myometrium during subacute, acute, and chronic administration of ethanol]. 1120 Apr 74

The subcommissural organ (SCO) of mammals is innervated by several neuropeptide and neurotransmitter systems. So far, substance P (SP), oxytocin (OXT), vasopressin (VP), somatostatin (SOM), thyrotropin-releasing factor (TRF), and angiotensin II (ANGII) were identified in neuropeptidergic input systems, and serotonin (5HT), gamma-amino butyric acid (GABA), noradrenaline (NA), dopamine (DA), and acetylcholine (Ach) were neurotransmitters observed in systems afferent to the SCO. In the present report, based on literature data and our own investigations, we describe the occurrence of peptide and transmitter receptors in the SCO by means of autoradiographic and biochemical studies. Further, we summarize aspects of the signal transduction cascades possibly linked to different receptor types of the SCO; these studies included the use of calcium imaging (FURA-2 technique), ELISA technique, and immunocytochemistry. Receptors were identified for adenosine, angiotensin II, imidazoline, glucocorticoids, mineralocorticoids, NA, and embryonic brain kinase. The studies on intracellular signal-transduction indicated receptors for tachykinins and for ATP. In SCO cells, Ca(++) and c-AMP were identified to act as second messengers. As important transcription factor, cAMP-/Ca(++)-response element binding protein (CREB) was observed. Ach and NA did not show a significant effect on the subcommissural signal transduction.
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PMID:Presence and functional significance of neuropeptide and neurotransmitter receptors in subcommissural organ cells. 1124 63


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