Biomedical subjects

Ismail H Ulus

Publications and source records attributed to Ismail H Ulus.

10 recordsLinked to original sources

PubMed2003

Intravenously injected CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock: effect is mediated by central cholinergic activation.

Intravenous (i.v.) administration of cytidine-5'-diphosphate choline (CDP-choline) (100, 250 and 500 mg/kg) increased blood pressure in normal rats and reversed hypotension in haemorrhagic shock. Choline (54 mg/kg; i.v.), at the dose equimolar to 250 mg/kg CDP-choline decreased blood pressure of rats in both conditions and caused the death of all hypotensive animals within 2-5 min. Equimolar dose of cytidine (124 mg/kg; i.v.) did not change cardiovascular parameters. Choline levels in plasma, lateral cerebral ventricle and hypothalamus increased after CDP-choline administration. Intracerebroventricular (i.c.v.) hemicholinium-3 pretreatment (20 microg), greatly attenuated the pressor effect of CDP-choline in both conditions. Atropine pretreatment (10 microg; i.c.v.) did not change the pressor effect of CDP-choline while mecamylamine (50 microg; i.c.v.) abolished the pressor response to drug. Besides, acetylcholine (1 micromol; i.c.v.) produced similar increases in blood pressure in normal and hypotensive conditions to that observed in CDP-choline given rats. CDP-choline (250 mg/kg; i.v.) increased plasma catecholamines and vasopressin levels but not plasma renin activity. Pretreatment of rats with either prazosin (0.5 mg/kg; i.v.) or vasopressin V(1) receptor antagonist, [beta-mercapto,beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2)-Arg(8)]vasopressin (10 microg/kg; i.v.), attenuated the pressor response to CDP-choline while simultaneous administration of these antagonists before CDP-choline injection completely blocked the pressor effect. Results show that i.v. CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock. Activation of central nicotinic cholinergic mechanisms by the increases in plasma and brain choline concentrations appears to be involved in the pressor effect of this drug. Moreover, the increases in plasma catecholamines and vasopressin levels mediate these effects.

Animals↗

PubMed2003

Serum free and phospholipid-bound choline decrease after surgery and methylprednisolone administration in dogs.

We designed this study to determine whether serum free and phospholipid-bound choline concentrations change after surgery or methylprednisolone treatment in dogs and rats. In dogs, serum free and phospholipid-bound choline concentrations were decreased by 29% and 17% immediately after abdominal-pelvic surgery under xylasine+ketamine anesthesia, respectively, and both remained low for 24 h. Serum cortisol was elevated after surgery. The elevation in serum cortisol was inversely correlated with the decreases in free (r=-0.737; P<0.001) and phospholipid-bound (r=-0.771; P<0.001) choline concentrations. After methyprednisolone administration (5-20 mg/kg) free and phospholipid-bound choline concentrations decreased in a dose- and time-dependent manner. In rats, either surgery or methylprednisolone failed to alter serum free choline concentrations while phospholipid-bound choline decreased after surgery. These data show that the decrease in serum choline after surgery results from the increase in circulating glucocorticoids.

Animals↗

PubMed2003

Choline increases serum insulin in rat when injected intraperitoneally and augments basal and stimulated aceylcholine release from the rat minced pancreas in vitro.

Intraperitoneal injection of choline (30-90 mg.kg-1) produced a dose-dependent increase in serum insulin, glucose and choline levels in rats. The increase in serum insulin induced by choline (90 mg.kg-1) was blocked by pretreatment with the muscarinic acetylcholine receptor antagonists, atropine (2 mg.kg-1), pirenzepine (2 mg.kg-1) and 4-diphenylacetoxy-N-methylpiperidine (2 mg.kg-1) or the ganglionic nicotinic receptor antagonist, hexamethonium (15 mg.kg-1). The effect of choline on serum insulin and glucose was enhanced by oral glucose administration (3 g.kg-1). Choline administration was associated with a significant (P < 0.001) increase in the acetylcholine content of pancreatic tissue. Choline (10-130 microm) increased basal and stimulated acetylcholine release but failed to evoke insulin release from the minced pancreas at considerably higher concentrations (0.1-10 mm). Hemicholium-3, a choline uptake inhibitor, attenuated the increase in acetylcholine release induced by choline augmentation. Choline (1-32 mm) inhibited [3H]quinuclidinyl benzilate binding to the muscarinic receptors in the pancreatic homogenates. These data show that choline, a precursor of the neurotransmitter acetylcholine, increases serum insulin by indirectly stimulating peripheral acetylcholine receptors through the enhancement of acetylcholine synthesis and release.

Acetylcholine↗

PubMed2003

Choline potentiates the pressor response evoked by glycyl-glutamine or naloxone in haemorrhaged rats.

1. Severe blood loss initially lowers arterial pressure through a central mechanism that is thought to involve opioid and cholinergic neurons. The present study tested the hypothesis that simultaneous administration of a cholinergic agonist and an opioid receptor antagonist would produce a synergistic effect in the treatment of haemorrhage. Specifically, we tested whether choline, a precursor of acetylcholine, potentiates the pressor effect of the beta-endorphin derived peptide glycyl-glutamine (Gly-Gln) or the opioid receptor antagonist naloxone following acute haemorrhage. 2. Conscious rats were treated intracerebroventricularly (i.c.v.) with choline chloride (180 nmol) alone or combined with Gly-Gln (10 nmol) or naloxone (10 nmol) 2 min after blood withdrawal (2.5 mL/100 g bodyweight over 20 min) was completed; mean arterial pressure and heart rate were monitored for 30 min. 3. Combined treatment with choline and Gly-Gln elevated mean arterial pressure but did not affect heart rate significantly. Choline and Gly-Gln had no effect on cardiovascular function when administered alone to haemorrhaged rats or when given together to normotensive animals. Choline also potentiated the pressor and tachycardic effect of naloxone in haemorrhaged rats. 4. These data show that choline potentiates the pressor effect of Gly-Gln and naloxone in haemorrhaged rats.

Animals↗

PubMed2002

Intracerebroventricular choline increases plasma vasopressin and augments plasma vasopressin response to osmotic stimulation and hemorrhage.

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.

Acetylcholine↗

PubMed2002

The decline in serum choline concentration in humans during and after surgery is associated with the elevation of cortisol, adrenocorticotropic hormone, prolactin and beta-endorphin concentrations.

Serum choline concentrations decrease during and after surgery. We undertook this study to determine whether the decrease of choline is associated with an increase in stress hormones. In 16 patients undergoing abdominal surgery with general anesthesia, circulating choline cortisol, prolactin, adrenocorticotropic hormone (ACTH) and -endorphin levels were measured before, during and after surgery. Choline levels decreased by 41% (P<0.01) during surgery, remained 15-38% decreased for 48 h, and returned to preoperative values 72 h after surgery. The decrease in serum choline was associated and inversely correlated with the increase in serum cortisol (P<0.001; r = -0.642), prolactin (P<0.001; r = -0.756), -endorphin (P<0.001; r = -0.726) and ACTH (P<0.01; r = -0.458). In conclusion, we found that abdominal surgery induces a decline in serum choline associated with an increase in circulating cortisol, prolactin, ACTH and -endorphin.

Acetylcholine↗

PubMed2002

Cardiovascular effects of intracerebroventricularly injected CDP-choline in normotensive and hypotensive animals: the involvement of cholinergic system.

Intracerebroventricular (i.c.v.) administration of CDP-choline (0.25, 0.5, 1 and 2 micromol) induced prompt, dose- and time-dependent increase in blood pressure in normotensive rats. Equimolar dose of CDP-choline (1 micromol; i.c.v.) and choline (1 micromol; i.c.v.) caused similar increases in blood pressure while cytidine (1 micromol; i.c.v.) failed to produce any pressor effect. In haemorrhagic shock, CDP-choline (0.1, 0.25, 0.5 and 1 micromol; i.c.v.) increased blood pressure dose- and time-dependently. The complete reversal of hypotension was observed with the i.c.v. injection of CDP-choline (1 micromol) and choline (1 micromol). Cytidine (1 micromol; i.c.v.) produced small, but significant ( P<0.05) increase in blood pressure in haemorrhaged rats. Dose-related bradycardia was observed with the injection of CDP-choline in normotensive rats, but the changes in heart rate were not significantly different ( P>0.05) in hypotensive conditions. Choline levels in lateral cerebral ventricle and hypothalamus increased about nine- and fivefold, respectively, after CDP-choline (1 micromol) administration in normotensive rats. In haemorrhagic shock extracellular choline levels in hypothalamus increased sevenfold after an i.c.v. administration of CDP-choline (1 micromol). Hemicholinium-3 (20 microg; i.c.v.), a neuronal high affinity choline uptake blocker, and mecamylamine (50 microg; i.c.v.), nicotinic receptor antagonist, pretreatment abolished the pressor effect of CDP-choline in normal rats. The increase in blood pressure was also attenuated by atropine (10 microg; i.c.v.) pretreatment. Atropine blocked the bradycardic response observed after CDP-choline. In haemorrhaged rats, the pressor effect of CDP-choline was attenuated by hemicholinium-3 and mecamylamine while atropine failed to alter the pressor response to CDP-choline. I.c.v. CDP-choline increased plasma adrenaline and vasopressin levels in normal rats. Haemorrhage, itself, increased plasma catecholamines and vasopressin levels. CDP-choline (1 micromol) produced additional increases in the elevated plasma levels of these hormones. An alpha(1)-adrenoceptor blocker, prazosin (0.5 mg/kg; i.v.), or vasopressin V(1) receptor antagonist, [beta-mercapto, beta,beta-cyclopenta-methylenepropionyl(1), O-Me-Tyr(2)-Arg(8)]-vasopressin (10 micro/kg; i.v.), pretreatments partially blocked the pressor response to CDP-choline (1 micromol; i.c.v.). Simultaneous administration of these two antagonists completely blocked the pressor effect of CDP-choline in haemorrhagic shock. These results show that the exogenous administration of CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock. In normotensive conditions, increase in blood pressure appears to be due to the activation of both nicotinic and muscarinic central cholinergic receptors through the activation of presynaptic cholinergic mechanisms. In hypotensive rats, activation of nicotinic cholinergic receptors is solely involved in the pressor effect. Increase in plasma vasopressin and adrenaline mediates the pressor response of CDP-choline in both normotensive and hypotensive conditions.

Animals↗

PubMed2002

Hyperglycemia induced by intracerebroventricular choline: involvement of the sympatho-adrenal system.

Intracerebroventricular (i.c.v.) injection of choline (75-300 microg) produced a dose-dependent increase in blood glucose levels. Pre-treatment with the nicotinic acetylcholine receptor antagonist, mecamylamine (50 microg, i.c.v.) blocked the hyperglycemia induced by choline (150 microg, i.c.v.), but the response was not affected by pre-treatment with the muscarinic acetylcholine receptor antagonist, atropine (10 microg, i.c.v.). Pre-treatment with the neuronal choline uptake inhibitor, hemicholinium-3 (20 microg, i.c.v.), attenuated the hyperglycemia induced by choline. The hyperglycemic response to choline was associated increased plasma levels of adrenaline and noradrenaline. The hyperglycemia elicited by choline was greatly attenuated by bilateral adrenalectomy, and entirely blocked by either surgical transection of the splanchnic nerves or by pre-treatment with the alpha-adrenoceptor antagonist, phentolamine. These data show that choline, a precursor of acetylcholine, increases blood glucose and this effect is mediated by central nicotinic acetylcholine receptor activation. An increase in sympatho-adrenal activity appears to be involved in the hyperglycemic effect of choline.

Adrenal Glands↗

PubMed2002

Changes of plasma free choline and choline-containing compounds' concentrations and choline loss during hemodialysis in ESRD patients.

OBJECTIVES: This study was undertaken to determine the changes in plasma free choline and choline-containing compounds in end stage renal disease (ESRD) and to determine if they were lost into the dialysate during hemodialysis. DESIGN AND METHODS: Plasma and dialysate free choline, phosphocholine and phospholipid-, phosphatidylcholine-, sphingomyelin-bound choline were measured before, during and after hemodialysis. RESULTS: Plasma free and bound choline concentrations (mean +/- standard error of the mean) were 12.9 +/- 0.6 and 2697 +/- 57 microM or 37.3 +/- 0.9 and 2792 +/- 98 microM in controls or in ESRD patients, respectively. Free choline concentrations were correlated (r = 0.598; p < 0.001) with the time the patients were subjected to hemodialysis. Plasma free choline and phosphocholine concentrations are decreased by a total of -8.1 +/- 0.6 micromol/L and -88 +/- 8 micromol/L, respectively; phospholipid-, phosphatidylcholine- and sphingomyelin-bound choline are increased, during hemodialysis. Patients lost about 350 micromoles of choline into the dialysate during hemodialysis. CONCLUSION: Plasma free choline concentrations are elevated in ESRD, and a considerable amount of choline is lost into the hemodialysate.

Adult↗

PubMed2002

Free choline and phospholipid-bound choline concentrations in serum and dialysate during peritoneal dialysis in children and adults.

OBJECTIVES: This study tested whether continuous ambulatory peritoneal dialysis (CAPD) changes free or phospholipid-bound choline concentrations in serum or peritoneal dialysis fluid of patients with end stage renal disease (ESRD). DESIGN AND METHODS: Serum and dialysate choline and phospholipid-bound choline were measured before, during and after 6 h CAPD. RESULTS: Serum choline concentrations were higher in patients with ESRD compared with age-matched controls. CAPD lowered serum choline concentrations significantly although it did not influence phospholipid-bound choline. Choline accumulated in the dialysate, reaching 28.4 +/- 2.7 microM in children and 18.2 +/- 1.4 microM in adults, during six hours CAPD; phospholipid-bound choline increased to 22.9 +/- 2.5 microM and 10.8 +/- 1.4 microM in children and adults, respectively. The total daily loss of choline into the dialysate was 181 +/- 20 micromoles in children and 260 +/- 18 micromoles in adults. CONCLUSION: CAPD causes a substantial loss of choline into peritoneal dialysates and reduces serum choline concentrations significantly.

Adolescent↗