Group totalling 55 young rabbits (both sexes), whose right optic nerves had been severed intraorbitally, were fed for 1 week, 2 weeks, 4 weeks and 8 weeks respectively. The retina of the left eye was used as a control and that of the right eye for the experiment. The histochemical changes of cholinesterase, acid phosphatase and ribonucleic acid in the reitna after to severance of the optic nerve were observed for 8 weeks after section. In the retina of the young rabbit, whose visual connection to the central nervous system was blocked, there was a decreasing specific cholinesterase activity beginning at the 4th week after the section of it. By the 8th week, the enzyme activity in the perikaryon of the ganglion cell and the inner plexiform layer was considerably decreased. Acid phosphatase activity in the young rabbit's retina peaked at the 2nd week, but decreaseed below normal after the 4th week. This rapid decline of acid phosphatase activity was characteristic in the experimental retinae and was in contrast to the rather slow alteration of enzymatic activity in neurons undergoing wallerian degeneration. Pyroninophilic granules contained in neural cytoplasm of the retina were affected by the surgical blocking of the visual connection with the central nervous system. By the 4th week the granules had partially disappeared from the perikaryon of the ganglion cell and from the inner nuclear layer. Consequently, as the result of histochemical studies, firstly it is postulated that the gradual decline of specific cholinesterase activity in the rabbit's retina was closely related to the intraorbital blocking of the optic nerve, and secondly, that the typical degeneration of the ganglion cell in the ganglion cell layer (which was associated with a partial disappearance of the ganglion cell) was related to the changes in the acid phosphatase activity and alteration of the pyroninophilic granules in the retina following optic nerve transection.
Acid Phosphatase/metabolism* ; Animal ; Cholinesterases/metabolism* ; Histocytochemistry ; Nerve Degeneration ; Neurons/enzymology ; Optic Nerve/surgery* ; Rabbits ; Retina/enzymology* ; Substances: ; Cholinesterases ; Acid Phosphatase

In the present study the specific and nonspecific cholinesterase activities of the rabbit's retinae in the fetus, the neonatal, the light-isolated, and the reopened group, which consisted of 65 healthy young rabbits, weighing about 300 to 500 gm, 33 rabbit's fetuses, and neonatal rabbits, were histochemically ovserved by means of the cholinesterase method recommended by Gerebtzoff (1953) and the embedding and sectioning method pesented by Koelle and Friedenwald (1950). Cholinesterase activity of the retinae in the 15 days fetuses was not present but began to develop in the 20 days fetuses. In the 1 week group after suturing the eyelids, the most remarkable activity of specific and nonspecific cholinesterase was observed in the posterior polar area. The nearer to the peripheral area of the retina the weaker the enzymetic activities became. In the 2 weeks group after suturing eyelids, the enzymatic activity was reduced. In the 4, and 8weeks groups after suturing the eyelides, the enzymatic activities were remarkably reduced. In the l4 days after reopening eyelide, which group has previously been kept under the condition of light isolation for 4 weeks, enzymatic activities were fairly recovered and compared with the normal control group. Consequently it is histochemically deduced that the gradual change of specific cholinesterase activities in the rabbit's retinae was closely related to the visual function.
Animals ; Animals, Newborn/enzymology ; Cholinesterases/*metabolism ; Histocytochemistry ; *Rabbits ; Retina/embryology/*enzymology

BACKGROUND: Cholinesterase inhibitors (ChEIs) which have been widely used clinically are known to have diverse actions on the neuromuscular synaptic transmissions, suggesting that inhibiting cholinesterase (ChE) might not be their only mode of action. ChEIs interact with the nicotinic acetylcholine receptor (nAChR) macromolecule as a weak agonist, and as a modulator inducing desensitization and blockade at high concentrations. In a previous study, we reported that carbamate ChEIs, Pyridostigmine and Physostigmine could facilitate the ionic influx through nAChRs, when precluding the Ach-hydrolyzing effect of acetylChE (AChE) by applying carbachol as an agonist. The facilitation of the nAChR function was supposed to be achieved by AChE-mediated nAChR modulation and possibly by the up-regulation of nAChRs. METHODS: In this study, we analyzed the effect of irreversible organophosphate ChEI, diisopropylfluorophosphate (DFP) on the function of muscular nAChRs in TE671 cells, quantifying carbachol-induced intracellular 22 Na+ influx through nAChRs, using radioassay. RESULTS: Preincubation of cells with 1 mM DFP at 37 degrees C for 10 min as well as the simultaneous application of carbachol and DFP, decreased the carbachol-induced influx dose-dependently.However, preincubation of cells with 10 micrometer DFP potentiated the influx to 132.5+/-7.4% CPM. Moreover, Najar Tx completely inhibited the potentiated 22 Na + influx. CONCLUSIONS: Organophosphate ChEI can facilitate nAChR functions at low concentrations with a yet discovered mechanism, which is supposed to necessitate cellular metabolism, and be possibly mediated by AChE. The inhibition of DFP on nAChR functions at high concentration is attributable to its remained curare-like actions and direct cellular toxicity.
Carbachol ; Cholinesterase Inhibitors ; Cholinesterases* ; Isoflurophate ; Metabolism ; Physostigmine ; Pyridostigmine Bromide ; Receptors, Nicotinic* ; Up-Regulation

BACKGROUND: Neostigmine, a cholinesterase inhibitor, is known to reverse the neuromuscular blocking action induced by nondepolarizing muscle relaxants at the end of general anesthesia. Some authors, however, reported that neostigmine has the properties of a neuromuscular block in skeletal muscles while others reported that neostigmine caused the smooth muscles such as the diaphragm to relax rather than to contract. The purpose of this study was to evaluate the effect of neostigmine at different doses on the tracheal smooth muscle in rabbits. METHODS: Isolated tracheal ring preparation in rabbits was used. Groups were divided into 7 groups; acetylcholine group (acetylcholine cumulative administered at doses of 10 8, 10 7, 10 6, 10 5, 10 4 and 10 3 M), neostigmine group (neostigmine cumulative administered at doses of 10 8, 10 7, 10 6, 10 5, 10 4 and 10 3 M), acetylcholine 10 6 M + neostigmine group (acetylcholine 10 6 M prior to neostigmine administered at doses of 10 8, 10 7, 10 6, 10 5, 10 4 and 10 3 M), acetylcholine 10 4 M + neostigmine group (acetylcholine 10 4 M prior to neostigmine administered at doses of 10 8, 10 7, 10 6, 10 5, 10 4 and 10 3 M), neostigmine 10 5, 10 4 and 10 3 M groups (neostigmine administered at doses of 10 5, 10 4 and 10 3 M). Smooth muscle contraction was evaluated in isometric tension per gram of tissue. RESULTS: In the acetylcholine group, the contractions increased as the dosage increased (10 8 10 3 M). In the neostigmine group, the contractions increased as the dosage increased (10 8 10 4 M), but at 10 3 M of neostigmine, contractions suddenly decreased. In addition when acetylcholine 10 6 M was given as a pretreatment, there was a sudden decrease in muscle contractions induced by neostigmine at 10 3 M. Also the contractions induced by 10 3 M neostigmine were less than that of 10 4 and 10 5 M. CONCLUSIONS: We concluded that neostigmine caused smooth muscle contraction at low concentrations by blocking acetylcholine metabolism, but at high concentrations, smooth muscle contractions were decreased and this might be due to direct action at the acetylcholine receptor.
Acetylcholine ; Anesthesia, General ; Cholinesterases ; Diaphragm ; Metabolism ; Muscle Contraction ; Muscle, Skeletal ; Muscle, Smooth* ; Neostigmine* ; Neuromuscular Blockade ; Rabbits*

The purpose of the present study was to investigate the effects of cornel iridoid glycoside (CIG) on the activity of cholinesterases in vitro, and to investigate the mechanism of CIG's treating Alzheimer's disease (AD). The sources of cholinesterases were prepared from human blood cells, rat brain homogenate and human blood plasma, respectively. The biochemical methods were used to detect the activity of acetylcholine esterase (AChE) and butyryl cholinesterase (BuChE) to investigate the influence of CIG on cholinesterases. The results showed that CIG inhibited the activity of AChE of human blood cells and rat brain homogenate, with the 50% inhibition rate (IC50) of 1.6 g . L-1 and 3.3 g . L-1, respectively; and the inhibition of AChE of CIG is reversible. CIG also inhibited the activity of BuChE of human blood plasma, with the IC50 of 2.9 g . L-1. In conclusion, CIG can inhibit the activity of AChE and BuChE in vitro, which may be one of the mechanisms of CIG to treat AD.
Acetylcholinesterase ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Cholinesterases ; metabolism ; Humans ; Iridoid Glycosides ; pharmacology ; Plasma ; enzymology ; Rats

Under the catalysis of a variety of metabolic enzymes in vivo, such as UDP-glucuronyl transferases, cytochrome P450, carboxylesterase, sulfotransferase, butyrylcholinesterase, catechol-O-methyl transferase and 6-morphine dehydrogenase, the drugs perform glucuronidation, hydrolysis, oxidation, sulfonation and other reactions, then translate into active or inactive metabolites, which are excreted through urination, bile or the other pathways at last. Different drugs own their different metabolic pathways. This paper introduces the studies about the metabolism of drugs in human and animal in recent years, such as morphine-like drugs, amphetamine, ketamine, cannabis and cocaine, and reviews the research progress about the sites of metabolism, metabolic enzymes, metabolites and physiological activity of those drugs metabolic in vivo.
Alcohol Oxidoreductases/metabolism* ; Animals ; Carboxylesterase/metabolism* ; Catechol O-Methyltransferase/metabolism* ; Cholinesterases/metabolism* ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Humans ; Illicit Drugs/metabolism* ; Oxidation-Reduction ; Sulfotransferases/metabolism*

BACKGROUND: Prolongation of the neuromuscular block of mivacurium can occur when there is a genetic deficiency of the enzyme or in the presence of anticholinesterase (AntiChE) which inhibit the activity of the enzyme. The aim of this study was to determine the efficacies of cholinesterase, AntiChE (neostigmine, pyridostigmine), and 4-aminopyridine in reversing mivacurium block, using the phrenic nerve-diaphragm preparation of a rat. METHODS: Forty-eight Sprague-Dawley rats (200~300 g) were anesthetized with peritoneal injection of 2.5% thiopental 5~10 ml. After a stable twitch and train-of-four responses were established for at least 30 minutes in each preparation, incremental dose of mivacurium was added to obtain 90~95% inhibition of control twitch height. The effects of 0.1 and 1.0 u/ml of horse pseudocholinesterase (pChE, Sigma), 0.1 and 1.0 g/ml of neostigmine, 0.2 and 2.0 g/ml of pyridostigmine, and 1.6, 16 g/ml of 4-aminopyridine (P.B.I) on reversal of mivacurium block were tested. The effects of 0.1 g/ml of neostigmine, or 0.2 g/ml of pyridostigmine with and without 0.1 or 1.0 u/ml of pChE following mivacurium were also tested. RESULTS: In reversing mivacurium block, single twitch and TOF ratios were recovered completely with pChE but not with antiChEs or 4-aminopyridine (p<0.05). Second set of experiments showed that antiChE mixed with pChE had a tendency to recover faster (p<0.05). The comparable recovery patterns of pChE 0.1u/ml alone and neostigmine 0.1 g/ml with pChE 0.1u/ml in our study, indicated that neostigmine would prolong the mivacurium block especially in the presence of hereditary or acquired defects of pChE activity. CONCLUSION: The authors conclude that pChE 1.0 u/ml with and without antiChE were equally effective in reversing neuromuscular block of mivacurium. If these results can be extrapolated to human, it is unlikely that mivacurium block is potentiated by antiChE that may slow its metabolism.
4-Aminopyridine* ; Animals ; Cholinesterases ; Diaphragm* ; Horses ; Humans ; Metabolism ; Neostigmine ; Neuromuscular Blockade* ; Pseudocholinesterase* ; Pyridostigmine Bromide ; Rats* ; Rats, Sprague-Dawley ; Thiopental

BACKGROUND/AIMS: Gastric peristalsis begins in the orad corpus and propagates to the pylorus. Directionality of peristalsis depends upon orderly generation and propagation of electrical slow waves and a frequency gradient between proximal and distal pacemakers. We sought to understand how chronotropic agonists affect coupling between corpus and antrum. METHODS: Electrophysiological and imaging techniques were used to investigate regulation of gastric slow wave frequency by muscarinic agonists in mice. We also investigated the expression and role of cholinesterases in regulating slow wave frequency and motor patterns in the stomach. RESULTS: Both acetycholinesterase (Ache) and butyrylcholine esterase (Bche) are expressed in gastric muscles and AChE is localized to varicose processes of motor neurons. Inhibition of AChE in the absence of stimulation increased slow wave frequency in corpus and throughout muscle strips containing corpus and antrum. CCh caused depolarization and increased slow wave frequency. Stimulation of cholinergic neurons increased slow wave frequency but did not cause depolarization. Neostigmine (1 muM) increased slow wave frequency, but uncoupling between corpus and antrum was not detected. Motility mapping of contractile activity in gastric muscles showed similar effects of enteric nerve stimulation on the frequency and propagation of slow waves, but neostigmine (> 1 muM) caused aberrant contractile frequency and propagation and ectopic pacemaking. CONCLUSIONS: Our data show that slow wave uncoupling is difficult to assess with electrical recording from a single or double sites and suggest that efficient metabolism of ACh released from motor neurons is an extremely important regulator of slow wave frequency and propagation and gastric motility patterns.
Animals ; Cholinergic Neurons ; Cholinesterases* ; Metabolism ; Mice* ; Motor Neurons ; Muscarinic Agonists ; Muscle, Smooth ; Muscles ; Neostigmine ; Peristalsis ; Pylorus ; Stomach

OBJECTIVETo explore the effect of hemoperfusion(HP) about the patients of methamidophos poisoning.

METHODSOn the basis of comprehensive treatment,15 cases of severe acute methamidophos poisoning patients were treated with HP, Blood samples were collected at 7 time points, before and 5, 15, 30, 45, 60mins following the beginning and the end of hemoperfusion. Blood samples were used for measuring the concentration of methamidophos and perfusion devices were used for measuring the volume of methamidophos adsorbed by the device after hemoperfusion.

RESULTS15 patients live in 12 cases, 3 cases of death. HP (former) blood Cholinesterase vigor were 662.60 + 632.05, HP (after) blood cholinesterase vigor were 2577.52 + 920.38 IU/L; The difference of blood Cholinesterase vigor between the before and after HP was statistically significant (P < 0.01). The patients' methamidophos concentration of blood when HP treated 45, 60, 120 min were respectively (851 + 672), (680 + 529), (587 + 520) microg /ml, there were significantly lower than that the patients' methamidophos concentration of blood who were before HP (1659 + 1105) microg/ml, a statistically significant difference (P < 0.01).

CONCLUSIONHP can be cut down obviously methamidophos poisoning patients serum concentrations of toxic, the experimental method directly prove the clinical application of carbon HP can really adsorption methamidophos.

Adult ; Cholinesterases ; metabolism ; Female ; Hemoperfusion ; methods ; Humans ; Insecticides ; poisoning ; Male ; Middle Aged ; Organothiophosphorus Compounds ; poisoning ; Treatment Outcome ; Young Adult

Pseudocholinesterase is known to be involved in the metabolism of succinylcholine, mivacurium, procaine, chloroprocaine, tetracaine, cocaine, heroin, and other drugs, although the physiologic function has not been well established. Prolonged neuromuscular block following administration of succinylcholine correlates with very low or genetically variant cholinesterase activity. The determination of pseudocholinesterase activity is of importance to the anesthetist in order to predict the susceptibility of the patient to the muscle relaxant, succinylcholine. The purpose of this study was to investigate the change of pseudocholinesterase level during cardiopulmonary bypass(CPB) for open heart surgery with hemodilution and hypothermia. Seven venous blood samples before induction of anesthesia(control), during CPB, and until the fifth postoperative day in 12 patients who underwent open heart surgery were taken. The pseudocholinesterase level was measured by Wako kit and JASCO UVIDEC 77 clinical spectrophotometer. The results were as follows ; 1) The control hematocrit was 40.32+/-6.21% and decreased to 23.72+/-1.86% immediately after the start of CPB(p<0.01) and to 22.42+/-1.93 % 30 minutes after the start of CPB(p<0.01). 2) The control pseudocholinesterase value of 1296.67+/-251.03 IU/L decreased to 915.67+/-228.16 IU/L immediately after the start of CPB(p<0.01), and to 727.83+/-197.58 IU/L 30 minutes after the start of CPB(p<0.01). 3) The mean values of pseudocholinesterase level immediately posteratively, on the first postoperative, and the third postoperative days were 1488.50+/-333.52 IU/L, 1913. 17+614.50 IU/L and 1620.92+/-458.82 IU/L, respectively, and those were significantly increased from the control value(p<0.05, p<0.01, and p<0.01, respectively). 4) The mean value of pseudocholinesterase level on the fifth postoperative day was 1392.25+/-271.69 IU/L, which was not significantly different from the control valule. 5) Transfused units of whole blood, packed red cells, and fresh frozen plasma were 2.8+/-1.4, 3.2 +/-1.0, 3.4+/-0.9, respectively.
Cardiopulmonary Bypass* ; Cholinesterases ; Cocaine ; Hematocrit ; Hemodilution ; Heroin ; Humans ; Hypothermia ; Metabolism ; Neuromuscular Blockade ; Plasma ; Procaine ; Pseudocholinesterase* ; Succinylcholine ; Tetracaine ; Thoracic Surgery