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)

The effects of several mediators including prostanoids, neuromediators, bioactive peptides and leukotrienes were investigated on the trachea, upper bronchi, lower bronchi and lung parenchyma of selected strains of mice mounted in a cascade superfusion system. The upper airways (trachea, upper bronchi) responded with greater maxima than lower airways (lower bronchi, lung parenchyma). Acetylcholine, carbachol, serotonin and 9, 11-dideoxy-9alpha,11alpha-epoxymethano-prostaglandin F(2alpha)serotonin>/=acetylcholine. Prostaglandins E(2), F(2alpha) and D(2)90% relaxation in some cases. The rank order of potency for the prostaglandins was E(2)>/=F(2alpha)D(2) with the exception of the lower bronchi on which prostaglandins had the following order of potency: F(2alpha)>/=E(2)D(2). The effects of prostaglandins were similar in four commonly used strains of mice (CD-1, BALB/c, C57BL/c6 and C3H) with some variations in efficacy. Iloprost was a weak mouse airway relaxant. It had the greatest effect on the trachea and bronchi of BALB/c and C57BL/c6 mice, whereas it had little or no effect on the airways of the CD-1 and C3H mouse strains. Vasoactive intestinal peptide potently relaxed the carbachol and precontracted the mouse trachea and bronchi. However, vasopressin, another bioactive peptide, potently and efficaciously contracted the mouse trachea and upper bronchi but had little effect on the lower bronchi. Vasopressin was the most potent and efficacious contractile agonist tested in this study. Contractions were observed with endothelins-1, -2 and -3 on mouse trachea and bronchi, but marked tachyphylaxis was present. Sarafotoxin s6c followed the same pattern suggesting the presence of endothelin ET(B) receptors on the mouse airways. Of all leukotrienes assayed (B(4), C(4), D(4) and E(4)) only leukotriene C(4) weakly contracted the mouse trachea and upper bronchi, but tachyphylaxis was most evident.
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PMID:Effects of eicosanoids, neuromediators and bioactive peptides on murine airways. 1068 88

The subfornical organ (SFO) is sensitive to both ANG II and ACh, and local application of these agents produces dipsogenic responses and vasopressin release. The present study examined the effects of cholinergic drugs, ANG II, and increased extracellular osmolarity on dissociated, cultured cells of the SFO that were retrogradely labeled from the supraoptic nucleus. The effects were measured as changes in cytosolic calcium in fura 2-loaded cells by using a calcium imaging system. Both ACh and carbachol increased intracellular ionic calcium concentration ([Ca2+]i). However, in contrast to the effects of muscarinic receptor agonists on SFO neurons, manipulation of the extracellular osmolality produced no effects, and application of ANG II produced only moderate effects on [Ca2+]i in a few retrogradely labeled cells. The cholinergic effects on [Ca2+]i could be blocked with the muscarinic receptor antagonist atropine and with the more selective muscarinic receptor antagonists pirenzepine and 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP). In addition, the calcium in the extracellular fluid was required for the cholinergic-induced increase in [Ca2+]i. These findings indicate that ACh acts to induce a functional cellular response in SFO neurons through action on a muscarinic receptor, probably of the M1 subtype and that the increase of [Ca2+]i, at least initially, requires the entry of extracellular Ca2+. Also, consistent with a functional role of M1 receptors in the SFO are the results of immunohistochemical preparations demonstrating M1 muscarinic receptor-like protein present within this forebrain circumventricular organ.
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PMID:Agonist activation of cytosolic Ca2+ in subfornical organ cells projecting to the supraoptic nucleus. 1129 85

The release of vasopressin and oxytocin from the supraoptic nucleus (SON) neurons is tonically regulated by excitatory glutamatergic and inhibitory GABAergic synaptic inputs. Acetylcholine is known to excite SON neurons and to elicit vasopressin release. Cholinergic receptors are located pre- and postsynaptically in the SON, but their functional significance in the regulation of SON neurons is not fully understood. In this study, we determined the role of presynaptic cholinergic receptors in regulation of the excitatory glutamatergic inputs to the SON neurons. The magnocellular neurons in the rat hypothalamic slices were identified microscopically, and the spontaneous miniature excitatory postsynaptic currents (mEPSCs) were recorded using the whole cell voltage-clamp technique. The mEPSCs were abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM). Acetylcholine (100 microM) significantly increased the frequency of mEPSCs of 38 SON neurons from 1.87 +/- 0.36 to 3.42 +/- 0.54 Hz but did not alter the amplitude (from 19.61 +/- 0.90 to 19.34 +/- 0.84 pA) and the decay time constant of mEPSCs. Furthermore, the nicotinic receptor antagonist mecamylamine (10 microM, n = 16), but not the muscarinic receptor antagonist atropine (100 microM, n = 12), abolished the excitatory effect of acetylcholine on the frequency of mEPSCs. These data provide new information that the excitatory effect of acetylcholine on the SON neurons is mediated, at least in part, by its effect on presynaptic glutamate release. Activation of presynaptic nicotinic, but not muscarinic, receptors located in the glutamatergic terminals increases the excitatory synaptic input to the SON neurons of the hypothalamus.
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PMID:Potentiation of glutamatergic synaptic input to supraoptic neurons by presynaptic nicotinic receptors. 1155 16

Both inhibitory GABAergic and excitatory glutamatergic inputs to supraoptic nucleus (SON) neurons can influence the release of vasopressin and oxytocin. Acetylcholine is known to excite SON neurons and to increase vasopressin release. The functional significance of cholinergic receptors, located at the presynaptic nerve terminals, in the regulation of the excitability of SON neurons is not fully known. In this study, we determined the role of presynaptic cholinergic receptors in regulation of the inhibitory GABAergic inputs to the SON neurons. The magnocellular neurons in the rat hypothalamic slice were identified microscopically, and the spontaneous miniature inhibitory postsynaptic currents (mIPSCs) were recorded using the whole-cell voltage-clamp technique. The mIPSCs were abolished by the GABA(A) receptor antagonist, bicuculline (10 microM). Acetylcholine (100 microM) significantly reduced the frequency of mIPSCs of SON neurons from 3.59+/-0.36 to 1.62+/-0.20 Hz (n=37), but did not alter the amplitude and the decay time constant of mIPSCs. Furthermore, the nicotinic receptor antagonist, mecamylamine (10 microM, n=13), eliminated the inhibitory effect of acetylcholine on mIPSCs of SON neurons. The muscarinic receptor antagonist, atropine (100 microM), did not alter significantly the effect of acetylcholine on mIPSCs in most of the 17 SON neurons studied. These results suggest that the excitatory effect of acetylcholine on the SON neurons is mediated, at least in part, by inhibition of presynaptic GABA release. Activation of presynaptic nicotinic receptors located in the GABAergic terminals plays a major role in the cholinergic regulation of the inhibitory GABAergic input to SON neurons.
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PMID:Acetylcholine attenuates synaptic GABA release to supraoptic neurons through presynaptic nicotinic receptors. 1171 21

Brain slice preparations preserving projections from nearby forebrain cholinergic neurons to the supraoptic nucleus (SON) were used to study synaptic potentials mediated by nicotinic acetylcholine receptors (nAChRs) in the hypothalamus. Paired-pulse electrical stimulation in an area anterior to the SON that was rich in cholinergic cells confirmed the monosynaptic nature of the connections to putative oxytocin and vasopressin SON neurons. With ionotropic glutamate and GABA(A) transmission blocked, this stimulation evoked fast, atropine-insensitive EPSPs that were sensitive to nAChR antagonists. Evoked EPSPs were blocked by methyllycaconitine and alpha-bungarotoxin, antagonists that are selective for nAChRs containing the alpha7 subunit, but not by dihydro-beta-erythroidine at concentrations known to antagonize alpha4beta2 nAChRs. Although anatomical evidence exists for postsynaptic alpha4beta2 nAChRs in the SON, these results indicate that postsynaptic alpha7 nAChRs are primarily responsible for the cholinergically mediated EPSPs. Repetitive stimulation suggested partial desensitization of the receptors. With ionotropic glutamate transmission blocked, inhibition of AChE increased spontaneous EPSP frequency and amplitude, suggesting spontaneous ACh release. ACh, nicotine, and choline (a selective alpha7 nAChR agonist) were effective in evoking action potentials and repetitive firing with synaptic transmission blocked by low Ca2+, high Mg2+ medium. These agonists were also effective in evoking the type of phasic bursts characteristic of vasopressin neurons, long thought to be completely dependent on activation of NMDA receptors (NMDARs). Because phasic bursting is Ca2+-dependent, the functional equivalence of alpha7 nAChR and NMDAR activation in this regard is likely attributable to their large Ca2+ fluxing capacities. This is the first demonstration that synaptically released ACh results in fast, alpha7 nAChR-mediated EPSPs in hypothalamic neurons.
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PMID:Synaptic potentials mediated by alpha 7 nicotinic acetylcholine receptors in supraoptic nucleus. 1175 85

The aim of the present work was to determine whether paraventricular neurons possess functional acetylcholine nicotinic receptors. Using infrared videomicroscopy and differential interference contrast optics, we performed whole-cell recordings in hypothalamic slices containing the paraventricular nucleus. Acetylcholine, locally applied by pressure microejection in the presence of the muscarinic antagonist atropine, evoked a rapidly rising inward current in paraventricular magnocellular endocrine neurons. This current persisted in the presence of blockers of synaptic transmission. It could be reversibly suppressed by nanomolar concentrations of methyllycaconitine, a selective antagonist of alpha 7-containing nicotinic receptors, but was insensitive to micromolar concentrations of dihydro-beta-erythroidine, an antagonist acting preferentially on non-alpha 7 nicotinic receptors. In addition, the effect of acetylcholine could be mimicked by exo-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane, a recently synthesized nicotinic agonist specific for alpha 7 receptors. Acetylcholine also desensitized paraventricular nicotinic receptors. Desensitization was pronounced and recovery from desensitization was rapid, consistent with the notion that paraventricular nicotinic receptors contain the alpha 7 subunit. Nicotinic currents could not be evoked in paraventricular parvocellular neurons, suggesting that these neurons are devoid of functional nicotinic receptors. The electrophysiological data were corroborated by light microscopic autoradiography, showing that [(125)I]alpha-bungarotoxin binding sites are present in all the magnocellular divisions of the paraventricular nucleus but are undetectable in other areas of this nucleus. Immunohistochemistry, performed using antibodies directed against vasopressin and oxytocin, indicated that responsiveness to nicotinic agonists was a property of vasopressin as well as of oxytocin magnocellular endocrine neurons, in both the paraventricular and the supraoptic nucleus. We conclude that nicotinic agonists can influence the magnocellular neurosecretory system by directly increasing the excitability of magnocellular neurons. By contrast, they are probably without direct effects on paraventricular parvocellular neurons.
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PMID:Nicotinic cholinergic activation of magnocellular neurons of the hypothalamic paraventricular nucleus. 1195 70

Acetylcholine produced a fall of blood eosinophils and adrenal ascorbic acid in normal rats; these effects did not occur in hypophysectomized animals or in hypophysectomized animals bearing a pituitary homotransplant in the anterior chamber of the eye. Acetylcholine had a striking and long-lasting antidiuretic effect in normal rats, which was abolished by hypophysectomy. In normal dogs, intravenous injections of acetylcholine raised the concentration of posterior pituitary antidiuretic hormone in the cerebrospinal fluid. These results are discussed in connexion with the hypothesis that posterior pituitary antidiuretic hormone may be the neurohumoral substance involved in the hypothalamic control of the anterior pituitary.
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PMID:Hypothalamo-neurohypophysial involvement in the corticotrophic action of acetylcholine. 1344 68

It has been previously shown that withdrawal from alcohol decreases the synthesis and expression of vasopressin (VP) and vasoactive intestinal polypeptide (VIP) in the suprachiasmatic nucleus (SCN), and that the infusion of NGF over 1 month completely restores these changes. Because SCN neurons do not express TrkA, NGF might have exerted its effects either through direct signalling of the neurons via p75NTR or by enhancing the activity of the cholinergic afferents to the SCN, which arise from the nucleus basalis magnocellularis (NBM). The observation that the infusion of NT-3 to withdrawn rats does not elicit any change in neuropeptide expression in the SCN suggests that ACh might be implicated in this process, a hypothesis that we have attempted to clarify in this study. For this purpose we destroyed, with quinolinic acid, the NBM of rats withdrawn from ethanol and later infused them with NGF over a period of 13 days. The total number and the somatic volume of SCN neurons immunoreactive for VP and VIP were stereologically estimated. No differences were found in the total number of neurons between quinolinic-injected NGF-treated withdrawn animals and intact withdrawn rats. However, the somatic volume of SCN neurons from quinolinic-injected animals was significantly reduced relative to control and withdrawn rats. The present results unequivocally demonstrate that the trophic effects exerted by NGF upon SCN neurons do not depend on direct neuronal signalling. Instead, they are indirect and, according to our results, NBM neurons, whose axons give rise to a cholinergic projection to the SCN, seem to be essential for eliciting those effects.
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PMID:The effects of nerve growth factor upon the neuropeptide content of the suprachiasmatic nucleus of rats withdrawn from ethanol are mediated by the nucleus basalis magnocellularis. 1552 May 30

Excessive exposure to glucocorticoids during gestation reduces birth weight and induces permanent hypertension in adulthood. The mechanisms underlying this programmed elevation of blood pressure have not been established. We hypothesised that prenatal glucocorticoid exposure may lead to vascular dysfunction in adulthood. Pregnant rats received dexamethasone (Dex) (100 microg/kg, s.c.) or vehicle (control) daily throughout pregnancy. Blood pressure was elevated (students t-test, unpaired; P < 0.05) in adult female offspring (aged 12-16 weeks) of Dex-treated mothers (148.0 +/- 3.6 mmHg, n=10) compared with the control group (138.0 +/- 2.5 mmHg, n=8). Vascular responsiveness in aortae and mesenteric arteries was differentially affected by prenatal Dex: aortae were less responsive to angiotensin II, whereas mesenteric arteries were more responsive to norepinephrine, vasopressin and potassium (mesenteric arteries respond poorly to angiotensin II in vitro). Acetylcholine-mediated, endothelium-dependent relaxation was similar in both groups. Prenatal exposure to Dex had no effect on blood pressure or aldosterone response to acute (15 min, i.v.) infusion of angiotensin II (75 ng/kg per min). In contrast, chronic (2-week, s.c.) infusion of angiotensin II (100 ng/kg per min) produced a greater elevation (P < 0.05) of blood pressure in Dex-treated rats (150.0 +/- 3.6 mmHg) than in controls (135.3 +/- 5.4 mmHg), and aldosterone levels were higher in Dex-treated animals. There was no angiotensin II-induced medial hypertrophy/hyperplasia in mesenteric arteries from Dex-treated rats. These results indicate that vascular function is altered in a region-specific manner in rats with glucocorticoid-programmed hypertension. Despite a striking increase in mesenteric artery contraction in Dex-treated rats, in vivo studies suggest that abnormalities of the renin-angiotensin-aldosterone system, rather than enhanced vascular contractility, may be responsible for the elevation of blood pressure in these animals.
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PMID:Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure. 1652 24

Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanine nucleotide-binding protein (G protein)-coupled receptors (GPCR). Examples of islet GPCR are GPR40 and GPR119, which are GPCR with fatty acids as ligands, the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the receptors for the islet hormones glucagon and somatostatin, the receptors for the classical neurotransmittors acetylcholine (ACh; M(3) muscarinic receptors) and noradrenaline (beta(2)- and alpha(2)-adrenoceptors) and for the neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP; PAC(1) and VPAC(2) receptors), cholecystokinin (CCK(A) receptors) and neuropeptide Y (NPY Y1 receptors). Other islet GPCR are the cannabinoid receptor (CB(1) receptors), the vasopressin receptors (V1(B) receptors) and the purinergic receptors (P(2Y) receptors). The islet GPCR couple mainly to adenylate cyclase and to phospholipase C (PLC). Since important pharmacological strategies for treatment of type 2 diabetes are stimulation of insulin secretion and inhibition of glucagon secretion, islet GPCR are potential drug targets. This review summarizes knowledge on islet GPCR.
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PMID:G-protein-coupled receptors and islet function-implications for treatment of type 2 diabetes. 1790 Jul


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