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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an isolated preparation of rat diaphragm stimulated indirectly (12 impulses per minute) after total inactivation of acetylcholinesterase phospholine reduced the amplitude of the response proportional to its concentration. The rise in the concentration of potassium, magnesium or calcium in the incubation fluid failed to alleviate the disturbances produced by phospholine. Phospholine increased significantly reduction of response amplitude caused by increased calcium and magnesium concentration and increased to a small extent response depression caused by raised potassium concentration. The obtained results, point out that phospholine exerts a direction on the neuromuscular junction which is connected with the postsynaptic action of this agent.
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PMID:The effect of certain electrolytes on neuromuscular transmission disturbances evoked by direct action of phospholine on synaptic structures. 626 79

The action of an irreversible inhibitor of acetylcholinesterase (AChE), the organophosphorus compound, ecothiopate iodide, and of a reactivator of phosphorylated AChE, contrathion, were analysed on acetylcholine (ACh) receptors and cholinergic synaptic transmission in the buccal ganglion of Aplysia. At high concentration (above 10(-4)mol X 1(-1), both compounds exerted a curare-like depression on ACh receptors which was reversible with washing. Both compounds reversibly facilitated the current response to ionophoretic application of ACh and increased the evoked postsynaptic current (PSC) as well as the miniature postsynaptic currents (MPSCs). All responses also showed an increase in decay time. These modifications, when induced by ecothiopate iodide were irreversible by washing; however they could be reversed if first washed with contrathion. Neither the organophosphate compound or the oxime did change the number of quanta released per impulse. The current response to ionophoretic application of carbachol also increased after ecothiopate iodide was added. In the limits of the method used, the conductance and opening time of postsynaptic ionic channels opened by ACh were not found to be modified by the two compounds. It was concluded that the facilitatory action of the organophosphorus inhibitors cannot be solely explained by the inhibition of ACh hydrolysis.
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PMID:Direct and indirect effects of an organophosphorus acetylcholinesterase inhibitor and of an oxime on a neuro-neuronal synapse. 630 Jul 51

Acetylcholine (ACh) content, release during stimulation and spontaneous leakage were studied at the diaphragm neuromuscular junction in rats aged 10 and 28 months. In addition, quantal release statistics were determined. The results were related to the number of nerve terminals per end-plate and to the age of the animals. Nerve terminal ACh content was lower in the 28-month-old rats; in nonstimulated tissue the average (+/- S.E.) ACh levels were 29.3 (+/- 4.1) and 17.2 (+/- 2.4) fmol per end-plate in the 10- and 28-month-old rats, respectively. During nerve stimulation, greater amounts of ACh were released by the older rats. After 1000 impulses, the average (+/- S.E.) ACh release was 3.2 (+/- 0.2) and 3.9 (+/- 0.2) fmol per end-plate in the 10- and the 28-month-old animals, respectively; however, the amounts released per nerve terminal were not significantly different. The fraction of the resting ACh content released per action potential was greater in the aged rats; this may be the cause of enhanced synaptic depression in the older animals. Leakage of ACh from cytoplasmic sources was assessed by measuring the hyperpolarization following application of d-tubocurarine (dTC). The hyperpolarizing responses were of similar magnitude in both age groups; however, the older rats were less sensitive to ACh, indicating that cytoplasmic leakage was greater in these animals. Miniature end-plate potentials (m.e.p.p.s) occurred twice as frequently in the aged rats; this increase could be attributed to an age-related increase in the number of nerve terminals per end-plate. After correcting for variations in membrane input resistance and resting potential, m.e.p.p. amplitudes were compared and found to be significantly smaller in the aged rats. Quantal release during nerve stimulation was measured and found to obey binomial statistics. Estimated values of m and n were significantly larger in the older rats; there were no age-related differences in p. The increases in m and n could be attributed to the larger number of nerve terminals per end-plate in the aged animals. Acetylcholinesterase (AChE) activity was assayed. In innervated tissue there were no significant differences with age; however, in non-innervated tissue AChE activity was significantly higher in the 28-month-old rats.
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PMID:Acetylcholine storage, release and leakage at the neuromuscular junction of mature adult and aged rats. 632 95

The actions of pyridostigmine (Pyr), an anticholinesterase agent, were studied on the acetylcholine (ACh) receptor-ion channel complex and on the electrically excitable membrane of the frog cutaneous pectoris and sartorius muscles and the chronically denervated soleus muscle of the rat. Pyr at concentrations of 0.2-0.4 mM potentiated the indirect evoked muscle twitch and at concentrations greater than or equal to 0.8 mM depressed the indirect twitch with an IC50 of about 2 mM. Twitch depression produced by Pyr was reversed slowly, and after a 60-min wash only 59% of the control muscle twitch had returned. Pyr did not affect either the membrane potential or the muscle action potential. Pyr had several effects at the neuromuscular junction of the frog and rat. It decreased the peak amplitude of the end-plate current (EPC) in a voltage- and concentration-dependent manner. In contrast to diisopropylfluorophosphate, which depresses the EPC amplitude and induces a double exponential decay of the EPC and miniature end-plate current (MEPC), Pyr produced a marked prolongation of the time constants of EPC and MEPC decay while maintaining a single exponential decay. The decrease caused by Pyr of indirect twitch tension, EPC amplitude, and ACh sensitivity indicates mechanisms which limit the number and/or properties of conducting channels. The drug decreased channel conductance and prolonged channel lifetime as revealed by Fourier analysis of ACh-induced end-plate current fluctuations. An altered form of the conducting species induced by Pyr appears to be responsible for either the apparent agonist-induced depolarization or its ability to increase the affinity of ACh for its recognition site. Pyr was also found to inhibit the binding of ACh and alpha-bungarotoxin to receptor-rich membrane from the electric organ of Torpedo nobiliana, and to have a higher affinity for the receptor than for the ion channel binding sites. These actions are distinct from acetylcholinesterase inhibition caused by the agent. Strong evidence suggests that the direct influences of the agent on neuromuscular transmission involve at least three distinct, although possibly interacting, mechanisms: (a) a weak agonist action, (b) the formation of desensitized receptor-complex intermediates, and (c) the alteration of the conductance properties of active channels.
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PMID:The nature of the interactions of pyridostigmine with the nicotinic acetylcholine receptor-ionic channel complex. I. Agonist, desensitizing, and binding properties. 632 55

Using diffusion chambers and short-term tissue culture, fragments from the supraoptic nucleus of the rat hypothalamus were cultivated. The tissue culture was studied by means of morphological, histological, autoradiographic, electron-microscopic and vital-microscopic techniques. The tissue culture was shown to possess neurosecretory cells containing acetylcholinesterase and responding to acetylcholine with changes of morphometric nuclear and cytoplasm indices, with depression of the secretory protein efflux to the incubation medium, and the decrease of H3-leucine and D-xylose influx to the cells.
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PMID:[Research on the anterior hypothalamic formations in tissue culture]. 651 May 27

A long-term epidemiological genetic study was conducted in which all new patients were evaluated prospectively at the Foundation for Depression and Manic Depression and two Lithium/Affective Disorders clinics at the Columbia-Presbyterian Medical Center between the years of 1972 and 1978. All patients met Feighner, RDC and DSM III criteria for Major Depressive Disorder after initial clinical screening interviews and were further subtyped using the Fieve-Dunner 7-point criteria. All 604 probands and 90% of 2711 first-degree relatives were interviewed blindly by diagnosticians trained in the use of the SADS structured interview. Cumulative morbid risk in parents, siblings and children of 490 bipolar probands was 15.6 +/- 3% and 14.0 +/- 1.7% in the first-degree relatives of 114 unipolar probands. A number of biological and genetic marker studies were simultaneously performed on samples of the overall population. The enzymes catechol O-methyltransferase and dopamine beta-hydroxylase, and the dexamethasone suppression test (SDT) did not show any biological marker value for outpatients even though both enzymes were determined to have hereditability. The HLA system, monoamine oxidase and acetylcholinesterase segregated differently from normal controls in samples of the patient population. The positive association findings with monoamine oxidase and the HLA system conflicted with the positive findings of other investigators, leaving doubtful their biological marker value. Red cell acetylcholinesterase was found to be significantly lower in affective disorder patients than in controls. This positive association finding was recently replicated by Mathews et al. (1982) but needs further confirmation. Using 28 blood group markers, a prior association study between the trait defining susceptibility to affective disorder and the genetic marker was positive for haptoglobin GC, and properdinfactor B, confirming earlier findings. Using the sib-pair method on the remaining 25 blood groups revealed that none other than peptidase A showed significant linkage with affective disorder since one significant finding is expected by chance. We conclude from the overall morbid risk data and segregation analyses that bipolar manic-depressive illness is a spectrum disease inherited through a multifactorial mode of genetic transmission (which is not synonymous with polygenetic inheritance) with possible genetic heterogeneity and find no evidence for X-linkage. Additional studies with acetylcholinesterase, haptoglobin, GC, and properdin-factor B are needed to confirm their positive biological/genetic marker value suggested by our long-term epidemiological study.
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PMID:Search for biological/genetic markers in a long-term epidemiological and morbid risk study of affective disorders. 651 12

Acetylcholinesterase (AChE) activity and protein were measured in the CSF of patients with Alzheimer's disease, depression, schizophrenia with and without tardive dyskinesia, and control subjects. AChE activity was assayed by a radioenzymatic method involving the direct extraction of hydrolyzed 3H-acetate into a toluene-based scintillation fluid followed by liquid scintillation spectrometry. AChE activity was proportional to the amount of CSF protein. Greater than 90% of AChE activity in CSF could be inhibited by 10(-3) M eserine. In addition, activity remained stable despite repeated freeze-thawing in an acetone-dry ice bath. Age was found to be positively correlated with CSF protein and AChE activity expressed per volume CSF, but not with AChE measured per milligram protein. No differences between diagnostic groups were found on either measure of AChE when the extraneous factors of age and CSF protein concentrations were controlled, nor were any differences found between groups for CSF protein when age was controlled.
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PMID:Acetylcholinesterase activity in CSF in schizophrenia, depression, Alzheimer's disease and normals. 666 67

Various doses of CBDP (2-(2- methylphenoxy )-4H-1,3,2- benzodioxaphosphorin -2-oxide), a metabolite of tri-o-cresyl phosphate, increased dramatically the acute toxicity of soman ( pinacolyl methylphosphonofluoridate ) in mice. CBDP (5 mg/kg; iv) reduced the soman LD50 value from 136 micrograms/kg in control to 6.95 micrograms/kg. The potentiation of soman toxicity following CBDP pretreatment appeared to be due primarily to inhibition of plasma aliesterase activity. Inhibition of liver aliesterase was not of primary importance in the potentiation of soman toxicity following CBDP pretreatment. In addition pretreatment with ISO-OMPA ( tetraisopropyl pyrophosphoramide ), a selective inhibitor of pseudocholinesterase, had no effect on the acute toxicity of soman. Similarly pretreatment of mice with pyridostigmine, a quaternary carbamate anticholinesterase which does not inhibit aliesterase , resulted in marked inhibition of diaphragm, plasma, and brain acetylcholinesterase had no effect on the acute toxicity of soman. Plasma aliesterase may be a depot for soman poisoning. The acute toxicity of soman by the ip, sc, and iv routes of administration was reduced following pretreatment of mice with phenobarbital (100 mg/kg) for 4 days. The reduced toxicity of soman following phenobarbital pretreatment was due to induction of liver aliesterase activity which subsequently resulted in an increase in plasma aliesterase activity. Thus more soman was probably bound to plasma aliesterase activity resulting in a reduction in acute toxicity of soman. Conversely pretreatment of mice with pentobarbital (70 mg/kg; ip) increased the toxicity of soman. This was probably the result of inhibition of plasma aliesterase by pentobarbital pretreatment combined with the central respiratory depression following pentobarbital administration. Following pentobarbital pretreatment soman inhibition of brain acetylcholinesterase was increased suggesting that plasma aliesterase inhibition alters the distribution of free soman in vivo. In summary, in mice plasma aliesterase appears to be an extremely important detoxification route for soman in vivo.
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PMID:Role of aliesterase in organophosphate poisoning. 672 16

Muscarinic receptors, [14C]choline uptake and acetylcholinesterase (AChE) activity in central and peripheral tissues of guinea-pigs treated repeatedly with diisopropylfluorophosphate (DFP) were simultaneously determined. After repeated DFP (1 mg/kg) administration, there was a significant decrease in specific [3H] quinuclidinyl benzilate binding only in the striatum, ileal longitudinal muscle and urinary bladder among various tissues examined. Scatchard analysis revealed that the administration of DFP at 0.5, 1 and 2 mg/kg which depressed the tissue AChE by 50 to 90%, caused a dose-dependent decrease (20-50%) in striatal and ileal [3H]quinuclidinyl benzilate binding sites without a change in the dissociation constant. The lower dose (0.2 mg/kg) of DFP depressed significantly the AChE in both tissues by 30% but failed to alter their [3H]quinuclidinyl benzilate binding sites. High affinity uptake of [14C]choline in the striatum and ileal longitudinal muscle was significantly decreased by repeated administration of DFP at 0.5 and 1 mg/kg but not 0.2 mg/kg. The DFP-induced loss of striatal and ileal muscarinic receptors was effectively antagonized by a concomitant administration of physostigmine (0.5 mg/kg) and atropine (5 mg/kg). Also, these drugs antagonized the DFP-induced decrease in the striatal [14C]choline uptake. Thus, the present study has demonstrated that repeated DFP administration causes a specific decrease in muscarinic receptors and [14C]choline uptake in the striatum and ileal longitudinal muscle of guinea pigs which is closely associated with a considerable (more than 50%) depression of the tissue AChE. In addition, these adaptive changes by DFP were effectively antagonized by physostigmine and atropine.
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PMID:Correlation between cholinesterase inhibition and reduction in muscarinic receptors and choline uptake by repeated diisopropylfluorophosphate administration: antagonism by physostigmine and atropine. 687 62

Repeated injection of paraoxon to pretrained rats 2 hr before avoidance sessions, at a dose causing considerable intoxication symptoms and reduction of brain acetylcholinesterase (0.125 mg/kg SC daily), induced marked performance depression followed by progressive development of tolerance. Additional groups treated either after each session (i.e., 23.5 hr before each subsequent session), or treated and not tested, showed a substantial depression when shifted to treatment 2 hr before sessions after achievement of tolerance by the animals tested from the beginning of the experiment at the time of maximal paraoxon effect. This indicates that chronic paraoxon tolerance cannot be ascribed entirely to metabolic and/or physiological changes occurring as a consequence of repeated treatment per se, but must be explained at least in part by postulating a behaviorally augmented (or "learned") component. In an additional experiment chronic paraoxon animals (0.1 mg/kg SC daily) were indistinguishable from control rats with respect to acquisition of light/go, noise-light/no go discrimination, i.e., of an active-passive avoidance task known to be highly sensitive to the disrupting (response-disinhibiting) effect of antimuscarinics. Therefore, the enhanced sensitivity to antimuscarinics in organophosphate tolerant rats, which is usually ascribed to cholinergic receptor changes, does not appear to be associated with a spontaneous "antimuscarinic-like" syndrome.
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PMID:Behaviorally augmented tolerance during chronic cholinesterase reduction by paraoxon. 709 54


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