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 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

The subfornical organ (SFO) has been suggested to be important for water intake and secretion of vasopressin (AVP). However, the role of the SFO cholinergic mechanism in the control of body fluid regulation is not clear. This study determined the effects of local cholinergic stimulation in the SFO produced by administration of physostigmine on drinking and cellular excitation in the anterior third ventricle (AV3V) region and in the supraoptic and paraventricular nuclei (SON and PVN). The results showed that injection of physostigmine into the SFO induced water intake and c-fos expression in the AV3V area as well as in the AVP containing neurons in the hypothalamus. Pretreatment of the SFO with mecamylamine, a nicotinic receptor antagonist, had no effect on physostigmine induced behavioral and c-fos responses. The muscarinic receptor blocker atropine, however, abolished both drinking and cellular activation after injection of physostigmine into the SFO. Immunostaining experiments demonstrated positive acetyltransferase (ChAT) in the SFO. Intensive ChAT immunoreactivity was located in the cholinergic fibers in the SFO. Together, the results indicate that SFO cholinergic mechanisms are important in co-operation with the AV3V and hypothalamic neurons in the control of thirst and AVP-mediated body fluid homeostasis.
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PMID:Functional relationship between subfornical organ cholinergic stimulation and cellular activation in the hypothalamus and AV3V region. 1174 49

The muscarinic receptor-mediated and non-muscarinic vascular effects of cholinomimetic drugs used in glaucoma were quantified. On the isolated rat aorta, the vascular tone induced by phenylephrine is functionally antagonized by cholinomimetic drugs. Based on EC50, the relative order of potency for the endothelium-dependent vascular relaxation was acetylcholine (0.05 microM) 1 > (+/-)-methacholine (0.35 microM) 1/7 > carbachol (0.63 microM) 1/12 > (+/-)-aceclidine (1.26 microM) 1/25. The maximal effects of the four agonists varied between 82-87%. The muscarinic vascular relaxation of 0.03 microM to 100 microM pilocarpine was less than 15%. At high concentrations, pilocarpine had 1/20.000 the vascular activity of acetylcholine. Physostigmine failed to potentiate the vascular relaxation of exogenous acetylcholine, indicating the absence of acetylcholine esterase in the tissue. Arecoline, with an EC50 of 7.76 microM, was partly sensitive to the removal of the endothelium. Atropine treatment did not block the vascular effect of high concentrations of pilocarpine. Atropine, as expected, blocked the vascular effects of carbachol with K(B) = 3.2 nM. Pilocarpine produces vascular relaxation by its competition with spasmogens like phenylephrine, oxymetazoline, vasopressin or latanoprost. Arecoline also shares these properties with pilocarpine in the blood vessel. The molecular mechanism of the vascular effects as well as ocular clinical implications of cholinomimetic drugs is discussed.
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PMID:Mechanism of vascular relaxation by cholinomimetic drugs with special reference to pilocarpine and arecoline. 1185 12

Intracerebroventricular (i.c.v.) injection of choline (50-150 microg), a precursor of the neurotransmitter acetylcholine, produced a time-and dose-dependent increase in plasma vasopressin levels in conscious, freely moving rats. The increase in plasma vasopressin in response to i.c.v. choline (150 microg) was inhibited by pretreatment with the nicotinic receptor antagonist, mecamylamine (50 microg; i.c.v.), but not by the muscarinic receptor antagonist, atropine (10 microg; i.c.v). The choline-induced rise in plasma vasopressin levels was greatly attenuated by hemicholinium-3 (HC-3; 20 microg; i.c.v.), a neuronal choline uptake inhibitor. Choline (50 or 150 microg; i.c.v.) produced a much greater increase in plasma vasopressin levels in osmotically stimulated or hemorrhaged rats than in normal rats. Choline (150 microg; i.c.v.) also enhanced plasma vasopressin response to graded hemorrhage; the enhancing effect of choline was also attenuated by HC-3 (20 microg; i.c.v.). Choline and acetylcholine concentrations in hypothalamic dialysates increased significantly following i.c.v. injection of choline (150 microg). It is concluded that choline increases plasma vasopressin levels by stimulating central nicotinic receptors indirectly, through the enhancement of acetylcholine synthesis and release, and augments the ability of osmotic stimulations or hemorrhage to stimulate vasopressin release.
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PMID:Intracerebroventricular choline increases plasma vasopressin and augments plasma vasopressin response to osmotic stimulation and hemorrhage. 1203 53

This review describes recent advances in our knowledge about the pathogenesis and therapeutic approaches to human gastric dysrhythmias. A number of clinical conditions has been found to be associated with gastric slow-wave rhythm disturbances that may relate to the induction of nausea and vomiting. Human and animal studies indicate that multiple neurohumoral factors are involved in the generation of gastric dysrhythmias. Antral distension and increased intestinal delivery of lipids may cause slow-wave disruption and development of nausea. This may be mediated by cholinergic and serotonergic pathways. Similarly, progesterone and estrogen may also disrupt gastric slow-wave rhythm in susceptible individuals. Prostaglandin overproduction in gastric smooth muscle appears to mediate slow-wave disruption in diabetes and with tobacco smoking. On the other hand, central cholinergic pathways play an important role in the genesis of gastric dysrhythmias associated with motion sickness. This may be mediated by vasopressin released from the pituitary. Although it is difficult to ascribe with certainty a causative role of slow-wave rhythm disturbances in the genesis of nausea and vomiting, the search has begun for novel antiemetic therapies based on their abilities to ablate or prevent gastric dysrhythmia formation. This includes the use of prostaglandin synthesis inhibitors, central muscarinic receptor antagonists, and dopamine receptor antagonists. Finally direct gastric electrical stimulation using a surgically implanted neurostimulator has shown promise in reducing emesis in patients with gastroparesis and gastric dysrhythmias.
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PMID:Physiology and pathophysiology of the interstitial cells of Cajal: from bench to bedside. VI. Pathogenesis and therapeutic approaches to human gastric dysrhythmias. 1206 86

In the present study, both the effects of intracerebroventricular (i.c.v.) injection of cytidine-5'-diphosphate choline (CDP-choline) on plasma vasopressin levels and the choline involvement of these effects were investigated. I.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 micromol) increased plasma vasopressin levels dose- and time-dependently. I.c.v. injection of equimolar dose of choline (1 micromol) produced similar vasopressin response. However equimolar dose of cytidine (1 micromol; i.c.v.), the other hydrolysis product of CDP-choline, did not affect plasma vasopressin levels. Pretreatment of rats with hemicholinium-3, neuronal high affinity choline uptake inhibitor (20 microg; i.c.v.) blocked the vasopressin response to i.c.v. CDP-choline (1 micromol). Pretreatment of rats with mecamylamine (50 microg; i.c.v.), a nonselective nicotinic receptor antagonist, abolished the increase in plasma vasopressin induced by CDP-choline while atropine (10 microg; i.c.v.), nonselective muscarinic receptor antagonist, failed to change the response. In conclusion, intracerebroventricularly injected CDP-choline can increase plasma vasopressin levels by activating central nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms.
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PMID:Centrally injected CDP-choline increases plasma vasopressin levels by central cholinergic activation. 1474 57

We aimed to investigate the effects of intracerebroventricularly (i.c.v.) injected glucagon-like peptide-1 (GLP-1) on blood pressure and heart rate, and whether central cholinergic system and vasopressinergic system play roles in these effects. Male Wistar albino rats were used throughout the experiments. Blood pressures and heart rates were observed before and for 30 min following drug injections. i.c.v. GLP-1 (100, 500 and 1000 ng/10 microl) caused a dose-dependent increase in both blood pressure and heart rate. Nicotinic receptor antagonist mecamylamine (25 microg/10 microl, i.c.v.) and muscarinic receptor antagonist atropine (5 microg/10 microl, i.c.v.) prevented the stimulating effect of GLP-1 on blood pressure. The effect of GLP-1 on heart rate was blocked only by mecamylamine. The V1 receptor antagonist of vasopressin (B-mercapto B, B-cyclopentamethylenepropionyl, O-Me-Tyr,Arg)-vasopressin (10 microg/kg), that was applied intraarterially, only prevented the effect of GLP-1 on blood pressure, but did not show any effect on heart rate. Our data indicate that i.c.v. GLP-1 increases blood pressure and heart rate, and stimulation of central nicotinic and partially muscarinic receptors and vasopressinergic system play a role in the effects of i.c.v. GLP-1 on blood pressure. The effect of GLP-1 on heart rate may be partially due to stimulation of central nicotinic receptors.
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PMID:Effects of intracerebroventricularly injected glucagon-like peptide-1 on cardiovascular parameters; role of central cholinergic system and vasopressin. 1475 54

1 Microinjection of peptide YY (PYY) (0.23-2.3 nmol) into the posterior hypothalamic nucleus (PHN) of conscious rats evokes a dose-dependent pressor response and a bradycardia. 2 The increase in mean arterial pressure evoked by 2.3 nmol of PYY was not blocked by intravenous pretreatment with: (i) the nicotinic ganglionic receptor antagonist pentolinium (PENT, 10 mg kg(-1)) alone, or in combination with the muscarinic receptor antagonist methylatropine (MeATR, 1 mg kg(-1)); (ii) the alpha(1)-adrenoceptor antagonist prazosin (PRAZ, 0.2 mg kg(-1)); (iii) the V(1)-vasopressin receptor antagonist [d(CH(2))(5)Tyr(Me)]AVP (AVPX, 20 microg kg(-1)); (iv) the combination of AVPX, PENT and MeATR; (v) the combination of PRAZ, AVPX, PENT, MeATR, and the alpha(2)-adrenoceptor antagonist yohimbine (0.3 mg kg(-1)); or (vi) the angiotensin II type 1 receptor antagonist ZD 7155 (1 mg kg(-1)). 3 Adrenal demedullation inhibited the PYY-evoked responses of drug-naive rats, and rats pretreated with the combination of PENT, MeATR and AVPX. 4 Transection of the splanchnic nerve innervating the adrenal medullae attenuated the bradycardia, as did ZD 7155, but not the PYY-evoked pressor response. 5 Systemic pretreatment of rats with the neuropeptide Y(1) receptor antagonist BIBP 3226 (1 mg kg(-1)) blocked the PYY-evoked cardiovascular changes, but not those evoked by microinjection of carbachol (5.5 nmol) into the PHN. 6 These results suggest that the cardiovascular changes evoked from the PHN by PYY requires the presence of the adrenal medullae, which are stimulated by: (i) a hormone to release an NPY-like substance that evokes the pressor response, and (ii) the splanchnic nerve to evoke the release of a substance that results in the bradycardia.
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PMID:Peptide YY administration into the posterior hypothalamic nucleus of the rat evokes cardiovascular changes by non-adrenergic, non-cholinergic mechanisms. 1575 5


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