Phentermine and other monoamine-oxidase inhibitors may increase plasma serotonin when given with fenfluramines.
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Analysis of Variance↗
Biomedical subjects
I H Ulus
Publications and source records attributed to I H Ulus.
The effects of choline on body temperature in conscious rats.
Choline (75-300 microg) produced dose-dependent hypothermia when injected intracerebroventricularly (i.c.v.). Pre-treatment with the muscarinic receptor antagonist, atropine (10 microg, i.c.v.), blocked the hypothermic effect of choline (150 microg), but the response was only partially attenuated by pre-treatment with the nicotinic receptor antagonist, mecamylamine (20 microg, i.c.v.). Pirenzepine (25 microg), a muscarinic M1 receptor antagonist, or hexahydro-siladifenidol (HHSD) (100 microg), a muscarinic M3 receptor antagonist, also blocked choline-induced hypothermia when injected centrally. Unlike the other muscarinic receptor antagonists, M2-selective 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyri do[2,3-b][1,4]benzodiazepin-6-one (AF-DX116) (10 microg), did not affect choline-induced hypothermia. We also found that choline-induced hypothermia was very sensitive to the ambient temperature. Similar to its effect at room temperature, choline produced dose-dependent hypothermia at 4 degrees C, but this effect was abolished at 32 degrees C. These data suggest that choline produces hypothermia and this effect is mediated by muscarinic receptors.
Acetylcholine↗
Cardiovascular effects of centrally injected tetrahydroaminoacridine in conscious normotensive rats.
In freely moving rats, intracerebroventricularly (i.c.v.) injected tetrahydroaminoacridine (10, 25, 50 microg) increased blood pressure and decreased heart rate in a dose- and time-dependent manner. Intravenous (i.v.) tetrahydroaminoacridine (1 and 3 mg/kg) also increased blood pressure. Atropine sulphate (10 microg; i.c.v.) pretreatment greatly attenuated the blood pressure response to i.c.v. tetrahydroaminoacridine while mecamylamine (50 microg; i.c.v.) failed to change the pressor effect. Neither atropine sulphate nor mecamylamine pretreatment affected the bradycardia induced by tetrahydroaminoacridine. However, the bradycardic response was completely blocked by atropine methylnitrate (2 mg/kg; i.p.) pretreatment. The pressor response to i.c.v. tetrahydroaminoacridine was associated with a several-fold increase in plasma levels of vasopressin, adrenaline and noradrenaline, but not of plasma renin. Pretreatment with prazosin (0.5 mg/kg; i.v.) attenuated the pressor effect without changing the bradycardia. Vasopressin V1 receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Me-Tyr2-A rg8]vasopressin (10 microg/kg; i.v.) pretreatment also partially inhibited the pressor response to i.c.v. tetrahydroaminoacridine and abolished the bradycardia. Tetrahydroaminoacridine's cardiovascular effects were completely blocked when rats were pretreated with prazosin plus vasopressin antagonist. The data show that tetrahydroaminoacridine increases blood pressure in normotensive freely moving rats by activating central muscarinic cholinergic transmission. Increases in plasma catecholamines and vasopressin are both involved in this response. The tetrahydroaminoacridine-induced reduction in heart rate appears to be due to the increase in vagal tone and plasma vasopressin.
Animals↗
Age-related alterations in pre-synaptic and receptor-mediated cholinergic functions in rat brain.
Fractional [3H]acetylcholine (ACh) release and regulation of release process by muscarinic receptors were studied in corpus striatum of young and aged rat brains. [3H] Quinuclidinyl benzilate (QNB) binding and carbachol stimulated phosphoinositide turnover, on the other hand, were compared in striatal, hippocampal and cortical tissues. High potassium (10 mM)-induced fractional [3H]ACh release from striatal slices was reduced by aging. Although inhibition of acetylcholinesterase with eserine (20 microM) significantly decreased stimulation-induced fractional [3H]ACh release in two groups of rats, this inhibition slightly lessened with aging. Incubation of striatal slices with muscarinic antagonists reversed eserine-induced inhibition in fractional [3H]ACh release with a similar order of potency (atropine = 4-DAMP > AF-DX 116 > pirenzepine) in young and aged rat striatum, but age-induced difference in stimulated ACh release was not abolish by muscarinic antagonists. These results suggested that fractional [3H]ACh release from striatum of both age groups is modulated mainly by M3 muscarinic receptor subtype. Although both muscarinic receptor density and labeling of inositol lipids with [myo-3H]inositol decreased with aging, carbachol-stimulated [3H]myo inositol-1-fosfat (IP1) accumulation was found similar in striatal, cortical and hippocampal slices.
Acetylcholine↗
Choline administration reverses hypotension in spinal cord transected rats: the involvement of vasopressin.
Intracerebroventricular (i.c.v.) choline (50-150 microg) increased blood pressure and decreased heart rate in spinal cord transected, hypotensive rats. Choline administered intraperitoneally (60 mg/kg), also, increased blood pressure, but to a lesser extent. The pressor response to i.c.v. choline was associated with an increase in plasma vasopressin. Mecamylamine pretreatment (50 microg; i.c.v.) blocked the pressor, bradycardic and vasopressin responses to choline (150 microg). Atropine pretreatment (10 microg; i.c.v.) abolished the bradycardia but failed to alter pressor and vasopressin responses. Hemicholinium-3 [HC-3 (20 microg; i.c.v.)] pretreatment attenuated both bradycardia and pressor responses to choline. The vasopressin V1 receptor antagonist, (beta-mercapto-beta,beta-cyclopenta-methylenepropionyl1, O-Me-Tyr2, Arg8)-vasopressin (10 microg/kg) administered intravenously 5 min after choline abolished the pressor response and attenuated the bradycardia-induced by choline. These data show that choline restores hypotension effectively by activating central nicotinic receptors via presynaptic mechanisms, in spinal shock. Choline-induced bradycardia is mediated by central nicotinic and muscarinic receptors. Increase in plasma vasopressin is involved in cardiovascular effects of choline.
Animals↗
Decreased serum choline concentrations in humans after surgery, childbirth, and traumatic head injury.
The serum levels of choline decreased by approximately 50% in patients having a surgery under general as well as epidural anesthesia. The decrease is lasts for two days after surgery. Intravenous administration of succinylcholine, either by a single bolus injection or by a slow continuous infusion, increased the serum choline levels several folds during surgery. In these patients, a significant decrease in the serum choline levels was observed one and two days after surgery. In 16 pregnant women at the term, serum choline levels were higher than the value observed in 19 nonpregnant women. The serum choline levels decreased by about 40% or 60% after having a childbirth either by vaginal delivery or caesarean section, respectively. Serum choline levels in blood obtained from 9 patients with traumatic head injury were significantly lower than the observed levels in blood samples obtained from healthy volunteers. These observations show that serum choline levels increase during pregnancy and decrease during stressful situations in humans.
Anesthesia, General↗
Centrally administered choline increases plasma prolactin levels in conscious rats.
Intracerebroventricular (i.c.v.) administration of choline, a precursor of acetylcholine (ACh) increased plasma prolactin levels in a time and dose-dependent manner in conscious rats. Pretreatment of rats with the cholinergic muscarinic antagonist, atropine (10 microg, i.c.v.), blocked the increase in plasma prolactin level. The increase was not influenced by pretreatment with the cholinergic nicotinic antagonist, mecamylamine (50 microg, i.c.v.). Pretreatment with hemicholinium-3 (HC-3; 20 microg, i.c.v.), a high affinity choline uptake inhibitor, attenuated the choline-induced increase of plasma prolactin levels. These results show that choline increases plasma prolactin levels by activating muscarinic receptors via presynaptic mechanisms.
Animals↗
Intracerebroventricular choline reverses hypotension induced by acute chemical sympathectomy.
1. The effect of centrally administered choline on blood pressure was investigated in rats made hypotensive by chemical sympathectomy. Chemical sympathectomy was produced by intravenous (i.v.) injection of 50 mg kg-1 of 6-hydroxydopamine (6-OHDA). Intracerebroventricular (i.c.v.) administration of choline (50-150 micrograms) 2 h after 6-OHDA treatment increased blood pressure and reversed the hypotension in a dose-dependent manner without affecting the heart rate. The pressor response was associated with an increase in plasma vasopressin levels. 2. Pretreatment of rats with the nicotinic receptor antagonist, mecamylamine (50 micrograms, i.c.v.), but not the muscarinic receptor antagonist atropine (10 micrograms, i.c.v.), blocked both the pressor and vasopressin responses to choline (150 micrograms). Pretreatment of rats with hemicholinium-3 (HC-3), a high affinity choline uptake inhibitor, greatly attenuated the pressor response to i.c.v. choline (150 micrograms). 3. The vasopressin V1 receptor antagonist, beta-mercapto-beta,beta-cyclopentamethylenepropionyl-O-Me-Try,Arg) - vasopressin (10 micrograms kg-1; i.v.) given 5 min after i.c.v. choline, decreased the blood pressure but failed to return it to the pre-choline levels. Prazosine (0.5 mg kg-1; i.p.), an antagonist of alpha-adrenoceptors, also decreased blood pressure. Administration of both antagonists together eliminated the pressor response to choline, and the blood pressure was reduced further to below the pre-choline levels. 4. It is concluded that i.c.v. choline can increase blood pressure in rats made hypotensive by acute chemical sympathectomy through the activation of central nicotinic receptors by presynaptic mechanisms. An elevation in plasma levels of both vasopressin and catecholamines (possibly released from the adrenal medulla) is involved in the pressor response to choline.
Adrenergic alpha-Antagonists↗
Cardiovascular effects of central choline during endotoxin shock in the rat.
The cardiovascular effects of intracerebroventricular (i.c.v.) administration of choline were studied in endotoxin-treated rats. Intravenous (i.v.) endotoxin (20 mg/kg) caused a moderate hypotension and tachycardia within 10 min of treatment. Choline (50, 100, and 150 microg; i.c.v.) increased blood pressure and decreased heart rate in this condition in a dose-dependent manner. Mecamylamine (50 microg; i.c.v.) pretreatment prevented the pressor and bradycardic responses to choline, whereas atropine (10 microg; i.c.v.) failed to alter both responses. Atropine pretreatment, alone, inhibited endotoxin-induced hypotension. The pressor responses to choline in endotoxin-treated rats were attenuated by pretreatment with hemicholinium-3 (20 microg; i.c.v.), a high-affinity neuronal choline-uptake inhibitor. Plasma vasopressin levels of endotoxin-treated rats were severalfold higher than those of control animals, and choline (50-150 microg; i.c.v.) produced further increases in plasma vasopressin in this condition. Mecamylamine abolished vasopressin response to endotoxin as well as to choline. The vasopressin receptor antagonist, (beta-mercapto-beta,beta-cyclopentamethylene-propionyl(1)-O-Me-Tyr2,Arg8 )-vasopressin (10 microg/kg; i.v.) administered 5 min after choline decreased blood pressure from the increased level to the precholine levels but did not alter bradycardia. These results indicate that, in rats treated with endotoxin, choline increases blood pressure and decreases heart rate by a presynaptic mechanism leading to the activation of central nicotinic cholinergic pathways. An increase in plasma vasopressin levels seems to be involved in the pressor, but not in the bradycardic response, to choline.
Animals↗
Metabotropic glutamate receptor agonists increase release of soluble amyloid precursor protein derivatives from rat brain cortical and hippocampal slices.
The proteolytic processing of the beta-amyloid precursor protein (APP) is regulated by neurotransmitters. Stimulation of metabotropic glutamate receptors (mGluRs) has been shown to increase the release of soluble amyloid precursor protein derivatives (APPs) from cultured cells. We examined the effects of mGluR agonists on APP processing in cortical and hippocampal slices from rat brain. Incubation of the slices in the presence of L-glutamic acid (500 microM), trans-(1S,3R)-1-amino-1,3-cyclopentane dicarboxylic acid (1-100 microM) or quisqualic acid (1-100 microM) increased APP release into the medium, relative to the amount of APPs released during incubation in normal Krebs-Ringer buffer under basal conditions. N-Methyl-D-aspartate (1-320 microM), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (1-100 microM) or kainic acid (5-500 microM) did not alter APP release. The increases in APP release induced by L-glutamic acid (500 microM), trans-(1S,3R)-1-amino-1,3-cyclopentane dicarboxylic acid (10 microM) or quisqualic acid (10 microM) were blocked by 100 microM (+/-)-alpha-methyl-4-carboxyphenylglycine, a selective antagonist of mGluRs. Incubation of the slices in the presence of 1 microM phorbol-12-myrisate-13-acetate, an activator of protein kinase C (PKC), also increased APP release, and an inhibitor of PKC, GF-109203X (1 microM), blocked this response as well as the release evoked by mGluR agonists. These data show that activation of mGluR increases APP release from brain slices via PKC-dependent mechanisms.
Alzheimer Disease↗
Central choline reverses hypotension caused by alpha-adrenoceptor or ganglion blockade in rats: the role of vasopressin.
The effect of intracerebrovenricularly (i.c.v.) injected choline on blood pressure was investigated in rats made hypotensive by blocking peripheral alpha-adrenoceptors or autonomic ganglionic transmission. Choline (50-150 micrograms; i.c.v.) increased blood pressure in a dose-dependent manner and 150 micrograms of choline restored blood pressure to the resting level. The pressor response to choline was associated with an increase in plasma vasopressin levels. Pretreatment with mecamylamine (50 micrograms; i.c.v.), but not atropine (10 micrograms; i.c.v.), blocked both the pressor and vasopressin responses to i.c.v. choline. The vasopressin receptor antagonist, [beta-mercapto-beta,beta-cyclopenta-methylene-propionyl1,O-Me-T ry2,Arg8] vasopressin (10 micrograms/kg; i.v.), given 5 min after i.c.v. choline (150 micrograms), abolished the pressor effect of choline and blood pressure returned to the pre-choline levels. It is concluded that the precursor of acetylcholine, choline, can increase blood pressure and reverse hypotension in alpha-adrenoceptor or ganglionic transmission blocked rats, by increasing plasma vasopressin.
Adrenergic alpha-Antagonists↗
Effect of intracerebroventricularly injected choline on plasma ACTH and beta-endorphin levels in conscious rats.
In the present study, we examined the effect of intracerebroventricularly injected choline on plasma ACTH (adrenocorticotrophin) and beta-endorphin levels in conscious rats. The intracerebroventricularly injection of choline (50-150 micrograms) elevated plasma ACTH levels in a dose-dependent manner. Plasma beta-endorphin levels were also significantly increased. Pretreatment of rats with mecamylamine (50 micrograms; intracerebroventricularly), the nicotinic receptor antagonist, completely inhibited the ACTH and beta-endorphin response to choline (150 micrograms; intracerebroventricularly). An antagonist of the muscarinic receptor, atropine (10 micrograms; intracerebroventricularly), failed to alter these effects. Pretreatment of rats with hemicholinium-3 (20 micrograms; intracerebroventricularly), a drug which inhibits the uptake of choline into cholinergic neurons, abolished the choline-induced increases in both plasma ACTH and beta-endorphin levels. These results indicate that choline can increase plasma concentrations of ACTH and beta-endorphin through the activation of central nicotinic acetylcholine receptors.
Adrenocorticotropic Hormone↗
Intracerebroventricular injection of choline increases plasma oxytocin levels in conscious rats.
In the present study, we examined the effect of intracerebroventricularly (i.c.v.) injected choline on both basal and stimulated oxytocin release in conscious rats. I.c.v. injection of choline (50-150 micrograms) caused time- and dose-dependent increases in plasma oxytocin levels under normal conditions. The increase in plasma oxytocin levels in response to i.c.v. choline (150 micrograms) was greatly attenuated by the pretreatment of rats with atropine (10 micrograms; i.c.v.), muscarinic receptor antagonist. Mecamylamine (50 micrograms; i.c.v.), a nicotinic receptor antagonist, failed to suppress the effect of 150 micrograms choline on oxytocin levels. Pretreatment of rats with 20 micrograms of hemicholinium-3 (HC-3), a specific inhibitor of choline uptake into nerve terminals, greatly attenuated the increase in plasma oxytocin levels in response to i.c.v. choline injection. Osmotic stimuli induced by either oral administration of 1 ml hypertonic saline (3 M) following 24-h dehydration of rats (type 1) or an i.c.v. injection of hypertonic saline (1 M) (type 2) increased plasma oxytocin levels significantly, but hemorrhage did not alter basal oxytocin concentrations. The i.c.v. injection of choline (50, 150 micrograms) under these conditions caused an additional and significant increase in plasma oxytocin concentrations beyond that produced by choline in normal conditions. These data show that choline can increase plasma oxytocin concentrations through the stimulation of central cholinergic muscarinic receptors by presynaptic mechanisms and enhance the stimulated oxytocin release.
Animals↗
3,4-Diaminopyridine and choline increase in vivo acetylcholine release in rat striatum.
We investigated the effects of choline, 3,4-diaminopyridine and their combination on acetylcholine release from the corpus striatum of freely moving rats which were treated or not with atropine. Intraperitoneal administration of choline or intrastriatal administration of 3,4-diaminopyridine increased acetylcholine levels in striatal dialysates in a dose-dependent manner. When 3,4-diaminopyridine treatment was combined with choline, the observed effect was considerably greater than the sum of the increases produced by choline or 3,4-diaminopyridine alone. Administration of atropine (1 microM) in the dialysing medium was also found to be effective to stimulate striatal acetylcholine levels. 3,4-Diaminopyridine did not affect acetylcholine levels under these conditions. Whereas the choline-induced increase in acetylcholine release was significantly potentiated by atropine, co-administration of 3,4-diaminopyridine with choline failed to produce a further significant increase in the presence of atropine. These results suggest that a highly effective means for increasing acetylcholine release involves two concurrent treatments that increase neuronal choline levels and inhibition of the negative feedback modulation of acetylcholine release.
4-Aminopyridine↗
Restoration of blood pressure by choline treatment in rats made hypotensive by haemorrhage.
1. Intracerebroventricular (i.c.v.) injection of choline (25-150 micrograms) increased blood pressure in rats made acutely hypotensive by haemorrhage. Intraperitoneal administration of choline (60 mg kg-1) also increased blood pressure, but to a lesser extent. Following i.c.v. injection of 25 micrograms or 50 micrograms of choline, heart rate did not change, while 100 micrograms or 150 micrograms i.c.v. choline produced a slight and short lasting bradycardia. Choline (150 micrograms) failed to alter the circulating residual volume of blood in haemorrhaged rats. 2. The pressor response to i.c.v. choline (50 micrograms) in haemorrhaged rats was abolished by pretreatment with mecamylamine (50 micrograms, i.c.v.) but not atropine (10 micrograms, i.c.v.). The pressor response to choline was blocked by pretreatment with hemicholinium-3 (20 micrograms, i.c.v.). 3. The pressor response to i.c.v. choline (150 micrograms) was associated with a several fold increase in plasma levels of vasopressin and adrenaline but not of noradrenaline and plasma renin. 4. The pressor response to i.c.v. choline (150 micrograms) was not altered by bilateral adrenalectomy, but was attenuated by systemic administration of either phentolamine (10 mg kg-1) or the vasopressin antagonist [beta-mercapto-beta,beta-cyclopenta-methylenepropionyl1, O-Me-Tyr2,Arg8]-vasopressin (10 micrograms kg-1). 5. It is concluded that the precursor of acetylcholine, choline, can increase and restore blood pressure in acutely haemorrhaged rats by increasing central cholinergic neurotransmission. Nicotinic receptor activation and an increase in plasma vasopressin and adrenaline level appear to be involved in this effect of choline.
Animals↗
Caffeine potentiates the enhancement by choline of striatal acetylcholine release.
We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.
Acetylcholine↗
N-methyl-D-aspartate increases acetylcholine release from rat striatum and cortex: its effect is augmented by choline.
We examined the effects of N-methyl-D-aspartate (NMDA), a glutamate agonist, and of glutamate itself, on acetylcholine (ACh) release from superfused rat striatal slices. In a Mg(++)-free medium, NMDA (32-1000 microM) as well as glutamate (1 mM) increased basal ACh release by 35 to 100% (all indicated differences, P less than .05), without altering tissue ACh or choline contents. This augmentation was blocked by Mg++ (1.2 mM) or by MK-801 (10 microM). Electrical stimulation (15 Hz, 75 mA) increased ACh release 9-fold (from 400 to 3660 pmol/mg of protein): this was enhanced (to 4850 pmol/mg of protein) by NMDA (100 microM). ACh levels in stimulated slices fell by 50 or 65% depending on the absence or presence of NMDA. The addition of choline (40 microM) increased ACh release both basally (570 pmol/mg of protein) and with electrical stimulation (6900 pmol/mg of protein). In stimulated slices choline acted synergistically with NMDA, raising ACh release to 10,520 pmol/mg of protein. The presence of choline also blocked the fall in tissue ACh. No treatment affected tissue phospholipid or protein levels. NMDA (32-320 microM) also augmented basal ACh release from cortical but not hippocampal slices. Choline efflux from striatal and cortical (but not hippocampal) slices decreased by 34 to 50% in Mg(++)-free medium. These data indicate that NMDA-like drugs may be useful, particularly in combination with choline, to enhance striatal and cortical cholinergic activity. ACh release from rat hippocampus apparently is not affected by NMDA receptors.
Acetylcholine↗
Release of vasopressin, cortisol and beta-endorphin in tetraplegic subjects in response to head-up tilt.
Plasma levels of beta-endorphin, vasopressin and cortisol during head-up tilt were measured in tetraplegic patients and in normal healthy subjects. In tetraplegic patients rapid tilt from the horizontal to 30 degrees or 60 degrees head-up induced orthostatic hypotension and increased plasma levels of cortisol, beta-endorphin and vasopressin. In control subjects head-up tilt failed to alter plasma levels of these hormones. These data show that the head-up position in tetraplegics causes various endocrine reactions.
Blood Pressure↗