Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to investigate whether cholinesterase (ChE) inhibitor exerts cardiovascular collapse through non-cholinergic mechanism in halothane-anesthetized rabbits. Physostigmine and N-methylcarbamate insecticides (BPMC = 2-sec-butylphenyl methylcarbamate and PHC = propoxur = 2-isopropoxyphenyl methylcarbamate) were employed as ChE inhibitors. Intravenous injection of physostigmine produced a dose-related pressor response a few minutes after the injection. In contrast, the injection of BPMC elicited a dose-related depressor response during the injection. PHC produced a slight depressor response during the injection followed by a dose-dependent pressor response. Norepinephrine (NE)-induced pressor response was inhibited by the ChE inhibitors with the same order and magnitude as the depressor response. ECG of physostigmine or PHC was characterized by an increase in QRS voltage and a sinus bradycardia, and that of BPMC by a decrease in QRS voltage. Atropine pretreatment inhibited the pressor response, the increase in QRS voltage and the sinus bradycardia, but not the depressor response and the decrease in QRS voltage. From these observations, it is suggested that the pressor response is ascribed to the cholinergic mechanism (acetylcholine accumulation through ChE inhibition), but the depressor response may result from a non-cholinergic mechanism. It is also suggested that the difference in the cardiovascular response is determined by a balance between cholinergic and non-cholinergic activity of each ChE inhibitor.
...
PMID:Cardiovascular collapse through non-cholinergic mechanism after intravenous injection of N-methylcarbamate insecticide in rabbits. 905 95

Tazarotene is a novel acetylenic retinoid for the treatment of psoriasis and acne. We examined (1) the hydrolysis of tazarotene in blood from Japanese-American and Caucasian subjects, (2) the esterases responsible for this hydrolysis in human blood, and (3) tazarotene hydrolysis in rat and human liver microsomes. Tazarotene hydrolysis and enzyme inhibition were assessed by monitoring the disappearance of tazarotene and the appearance of its primary metabolite tazarotenic acid by HPLC. In blood, tazarotene was converted mainly to tazarotenic acid via first-order kinetics, and there was no statistically significant difference in the hydrolytic (metabolic) rate of tazarotene in uninhibited Japanese-American and Caucasian blood. Physostigmine (a cholinesterase inhibitor), bis(p-nitrophenyl) phosphate (a carboxylesterase inhibitor), and EDTA (an aromatic esterase inhibitor) did not significantly affect tazarotene hydrolysis in blood. Paraoxon, an inhibitor of all serine esterases including cholinesterase and carboxylesterase, decreased the hydrolysis of tazarotene to tazarotenic acid by 95% in both blood and liver microsomes. In conclusion, blood and liver esterases play a significant role in the hydrolysis of tazarotene to tazarotenic acid, and paraoxon-inhibitable forms of esterases are involved in this hydrolysis in humans.
...
PMID:Metabolic deesterification of tazarotene in human blood and rat and human liver microsomes. 926 78

These experiments tested the role of cholinergic mechanisms in the changes of cerebral cortical blood flow (CBF) induced by brain trauma. CBF was measured with Iodo-14C-antipyrine autoradiography, in 128 cerebral cortex regions of both hemispheres, distributed in eight coronal slices. The effects of a 6.3-mm diameter craniotomy over the left motor-sensory cortex with no weight drop, and of trauma (drop weight of 20 g from 30 cm height on left motor-sensory cortex through a 6.3 mm circular craniotomy) on CBF were studied at 2 and 24 h after the interventions. A group of control animals that received no intervention was also set up. Animals were treated with the cholinesterase inhibitor physostigmine salicylate (3.3 microg/kg/min i.v. infusion started 60 min before CBF measurements), the cholinergic blocker scopolamine hydrobromide (1 mg/kg i.v. pulse, 18 min before CBF measurements), or with the drugs vehicle (saline). A focus of decreased CBF at the site of impact was observed 2 h after trauma, extending caudally as far as the occipital cortex. CBF on the contralateral cerebral cortex was also decreased. Both phenomena reversed partially at 24 h. This spontaneous recovery of CBF was blocked by scopolamine. Physostigmine reversed the decrease in CBF of the traumatized cortex, partially around the contused area and completely in more distant regions. The cerebral cortex contralateral to the trauma showed significantly higher CBF 24 h after trauma when compared to intact controls or craniotomy that peaked at the area symmetrical to the center of trauma. This phenomenon was also enhanced by physostigmine and completely blocked by scopolamine. These results suggest a prominent role of cholinergic mechanisms in the vascular adjustments that accompany cerebral trauma.
...
PMID:Cholinergic modulation of cerebral cortical blood flow changes induced by trauma. 930 May 67

Physostigmine, a powerful cholinesterase inhibitor, has recently been labelled with 11C in view of its potential application for in vivo imaging of cerebral acetylcholinesterase (AChE) using positron emission tomography. Here we carried out autoradiography of the rat brain using [11C]physostigmine in order to characterize the cerebral targets of this ligand. Autoradiograms were obtained using phosphor storage plates which, compared to autoradiographic films, greatly improved the quality of 11C images. Following autoradiography, brain sections were stained for AChE activity, allowing a direct comparison of autoradiographic and histoenzymatic localizations. The distributions of 11C label and of AChE activity were found to be essentially super-imposable, both after in vivo injection of and after in vitro incubation with [11C]physostigmine. Densitometric analysis showed that radioactivity and enzymatic activity distributions were regionally correlated. The fixation of [11C]physostigmine to cerebral tissue was abolished after incubation of the rat brain sections with BW 284C51, a specific AChE inhibitor, but not after incubation with iso-OMPA, a specific inhibitor of butyrylcholinesterase. Unilateral excitotoxic lesions of the striatum that eliminated local AChE expression concomitantly reduced the binding of the ligand in the lesioned area. These results indicate that autoradiographic images of the rat brain obtained with [11C]physostigmine reflect AChE distribution, thus supporting the use of this radioligand to trace cerebral AChE activity in humans with positron emission tomography.
...
PMID:Rat brain acetylcholinesterase visualized with [11C]physostigmine. 934 68

Glucose utilization of four cerebral cortex and 35 subcortical regions (CGU) was analyzed in three models of cholinergic seizures induced by the following compounds: 1) soman (pinacolylmethylphosphonofluoridate) an organophosphorus cholinesterase inhibitor, 100 microg/kg SC after pretreatment with pyridostigmine 26 microg/kg IM (n = 6); 2) physostigmine, a carbamate cholinesterase inhibitor, 1.31 mg/kg infused IV over 75 min (n = 6); and 3) pilocarpine, a direct cholinergic agonist, 30 mg/kg SC (n = 6). Physostigmine and pilocarpine were preceded by 3 mmol/kg LiCl IP 20 hrs earlier. Animals injected with saline SC (n = 6) were used as controls. Step-wise discriminant analysis successfully classified 100% of the cases into the four experimental groups with data from only six regions. Pyridostigmine-soman induced the most widespread and greatest increases in CGU. More restricted and lower levels of activation were observed with Li-pilocarpine while Li-physostigmine induced significant increases in CGU only in globus pallidus, entopeduncular nucleus, and substantia nigra. These three regions, which are functionally related, were also activated in the other two models of cholinergic convulsions and may represent the initial step in cholinergic activation of the CNS. Li-pilocarpine failed to activate most of the brainstem and the superior colliculus. All cortical regions were activated by Li-pilocarpine and pyridostigmine-soman, while they were inhibited by Li-physostigmine. This phenomenon may be due in part to the lack of activation with physostigmine of the basal forebrain nuclei (lateral septum, medial septum, vertical and horizontal limbs of the diagonal band, and substantia innominata) resulting in a decreased drive of cortical metabolism.
...
PMID:Mapping of cerebral metabolic activation in three models of cholinergic convulsions. 944 35

1. We investigated whether change in neuronal activity in cholinergic pathways mediates the anesthetic effect of the alpha2 agonist, dexmedetomidine, by determining whether physostigmine, a cholinesterase inhibitor, could antagonize the hypnotic response to dexmedetomidine in the rat and whether dexmedetomidine decreases the release of acetylcholine (ACh) in the thalamus in vivo. 2. Physostigmine did not significantly change the duration of the hypnotic response to dexmedetomidine. There was no significant change in thalamic ACh release after administration of dexmedetomidine. Therefore, alpha2-adrenergic agonists produce their anesthetic effect through mechanisms which do not involve alteration of the activity of the brainstem cholinergic nuclei.
...
PMID:Are cholinergic pathways involved in the anesthetic response to alpha2 agonists. 1004 39

Acetylcholine is found within key sectors of the olfactory pathway, and is the neurotransmitter for many bulbopetal axons terminating in the glomerular and internal plexiform layers of the olfactory bulb. The present study determined whether systemically administered physostigmine, a cholinesterase inhibitor, alters the rat's ability to discern among odorant mixtures. Following appropriate training, the performance of eight rats was measured every third day on an odor mixture discrimination test with six levels of difficulty. On each test day (separated from one another by 3 days), a different drug treatment was administered [i.e., 0.00 (saline), 0.05, 0.10, or 0.20 mg/kg physostigmine]. The presentation order of the treatments was counterbalanced across subjects using 4 x 4 Latin squares. The mixture discrimination test consisted of discerning the odor of an airstream coming from the saturated head space of a 1% concentration of ethyl acetate from an airstream saturated with a 1% concentration of ethyl acetate and various concentrations of butanol (i.e., 1, 0.5, 0.1, 0.05, 0.01, or 0.005%). Physostigmine was found to enhance odor discrimination performance on the more difficult discrimination tasks in a dose-related manner, suggesting that cholinergic activation may sharpen the ability of rats to discern subtle differences among complex odor stimuli.
...
PMID:Physostigmine enhances performance on an odor mixture discrimination test. 1007 83

Animal studies indicate that central cholinergic neurotransmission stimulates CRH secretion, but several human studies suggest that the hypothalamo-pituitary-adrenal cortical (HPA) axis may be activated only by doses of cholinergic agonists that produce noxious side effects and, by inference, a nonspecific stress response. Physostigmine (PHYSO), a reversible cholinesterase inhibitor, was administered to normal women and men at a dose that elevated plasma ACTH1-39, cortisol, and arginine vasopressin (AVP) concentrations but produced few or no side effects. Exogenous AVP also was administered alone and following PHYSO, to determine if it would augment the effect of PHYSO on the HPA axis. Fourteen normal women and 14 normal men matched to the women on age and race underwent four test sessions 5 to 7 days apart: PHYSO (8 micrograms/kg i.v.), AVP (0.08 U/kg i.m.), PHYSO plus AVP, and saline control. Serial blood samples taken before and after pharmacologic challenge were analyzed for ACTH1-39, cortisol, and AVP. PHYSO and AVP administration produced no side effects in about half the subjects and mild side effects in the other half, with no significant female-male differences overall. There also were no significant female-male differences in ACTH1-39 or cortisol responses to AVP. In contrast, the men had significantly greater ACTH1-39 responses to PHYSO administration than did the women. The endogenous AVP response to PHYSO also was significantly greater in the men than in the women, and the ACTH1-39 and AVP responses to PHYSO were significantly correlated in the men (both = +0.70) but not in the women. None of the hormone responses was significantly correlated with the presence or absence of side effects in either group of subjects. These results indicate a greater sensitivity of the HPA axis to low-dose PHYSO in normal men than in normal women, which likely is mediated by increased secretion of AVP. The lack of difference in side effects between the two groups of subjects and the lack of significant correlations between presence or absence of side effects and hormone responses in either group suggest that the increased hormone responses in the men were due to increased responsivity of central cholinergic systems and not to a nonspecific stress response.
...
PMID:Pituitary-adrenal cortical responses to low-dose physostigmine and arginine vasopressin administration in normal women and men. 1019 24

The luminal and mucosal deesterification of the prodrug ester cefpodoxime-proxetil was studied in human duodenal washings in vitro. Enzymatic hydrolysis of the ester, releasing the active third generation cephalosporin, was observed in luminal washing in the same way as it had previously been observed in the rabbit. Eserine and PMSF and HgCl(2) were potent inhibitors of cefpodoxime-proxetil hydrolysis in luminal washing, suggesting the participation of a cholinesterase in the hydrolysis of cefpodoxime-proxetil. These results are in agreement with our previous findings performed in the rabbit. Moreover, cefpodoxime-proxetil directly decreases the acetylcholinesterase activity when tested by a specific enzymatic method. These observations support the hypothesis that the partial oral bioavailability of cefpodoxime-proxetil results from hydrolysis by luminal cholinesterases. In vitro experiments run with rabbit duodenal washing with food components were compared with the pharmacokinetics of cefpodoxime-proxetil in humans. Amino acids, trace elements and vitamins were potent inhibitors for cefpodoxime-proxetil hydrolysis in duodenal washings. Otherwise, lipids (LTC and mixed LCT/MCT) did not interact. In the human, cefpodoxime-proxetil bioavailability is significantly enhanced when tablets are administered with food. The correlation found between animal results and human results in vitro for prospective investigation of a new prodrug ester could be very useful. An in vitro hydrolysis in intestinal animal washings could allow the potentially degraded condition and the food effect of the luminal tract to be assessed before absorption.
...
PMID:Cefpodoxime-proxetil hydrolysis and food effects in the intestinal lumen before absorption: in vitro comparison of rabbit and human material. 1047 12

Previous studies indicate cholinergic systems suppress somatic nociception. The present studies determined if cholinergic muscarinic systems suppress visceral nociception, specifically, chemical irritation of the lower urinary tract. Bladders of urethane-anesthetized rats were cannulated through the dome for continuous-infusion cystometrogram recordings. EMG electrodes recorded anal sphincter activity. Infusion of 0.5% acetic acid into the bladder to produce irritation increased bladder activity and anal sphincter activity (i.e. activation of a nociceptive vesicoanal reflex). Oxotremorine (a muscarinic agonist) and (-)butylthio[2.2.2] (a mixed muscarinic agonist/antagonist) dose-dependently inhibited vesicoanal reflex activity. This inhibition was antagonized by atropine (a centrally active muscarinic antagonist) but not by scopolamine methylbromide (a peripherally restricted muscarinic antagonist). Physostigmine (a centrally active cholinesterase inhibitor) also dose-dependently inhibited vesicoanal reflex activity in an atropine-sensitive manner, while neostigmine (a peripherally restricted cholinesterase inhibitor) did not. Atropine alone (i.e. administered without prior administration of muscarinic agonist or cholinesterase inhibitor) produced robust but transient (15 min) increases in vesicoanal activity and bladder activity under conditions of acetic acid infusion into the bladder. Under conditions of saline infusion into the bladder, atropine had the opposite effect on bladder activity (i.e. inhibition). These studies indicate that an endogenous cholinergic muscarinic system can be activated by lower urinary tract irritation to suppress visceral nociception through central nervous system mechanisms.
...
PMID:Central muscarinic inhibition of lower urinary tract nociception. 1086 9


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---