Effect Of Eserine Research Articles

Ovariectomy reduces cholinergic modulation of excitatory synaptic transmission in the rat entorhinal cortex

Estrogens are thought to contribute to cognitive function in part by promoting the function of basal forebrain cholinergic neurons that project to the hippocampus and cortical regions including the entorhinal cortex. Reductions in estrogens may alter cognition by reducing the function of cholinergic inputs to both the hippocampus and entorhinal cortex. In the present study, we assessed the effects of ovariectomy on proteins associated with cholinergic synapses in the entorhinal cortex. Ovariectomy was conducted at PD63, and tissue was obtained on PD84 to 89 to quantify changes in the degradative enzyme acetylcholinesterase, the vesicular acetylcholine transporter, and muscarinic M1 receptor protein. Although the vesicular acetylcholine transporter was unaffected, ovariectomy reduced both acetylcholinesterase and M1 receptor protein, and these reductions were prevented by chronic replacement of 17β-estradiol following ovariectomy. We also assessed the effects of ovariectomy on the cholinergic modulation of excitatory transmission, by comparing the effects of the acetylcholinesterase inhibitor eserine on evoked excitatory synaptic field potentials in brain slices obtained from intact rats, and from ovariectomized rats with or without 17β-estradiol replacement. Eserine is known to prolong the effects of endogenously released acetylcholine, resulting in an M1-like mediated reduction of glutamate release at excitatory synapses. The reduction in excitatory synaptic potentials in layer II of the entorhinal cortex induced by 15-min application of 10 μM eserine was greatly reduced in slices from ovariectomized rats as compared to intact rats and ovariectomized rats with replacement of 17β-estradiol. The reduced modulatory effect of eserine is consistent with the observed changes in cholinergic proteins, and suggests that reductions in 17β-estradiol following ovariectomy lead to impaired cholinergic function within the entorhinal cortex.

Evaluation of the effects of Eserine and JWH-133 on brain dysfunction associated with experimental endotoxemia.

Sepsis is associated with neuronal damage and cognitive impairment, with the participation of pro-inflammatory cytokines and oxidative-nitrous stress. It is known that activated microglia plays a vital role in neuro-inflammation and neuro-degeneration. Thus, the objective of this study was to evaluate therapeutic roles of two microglia regulating agents, JWH-133 and Eserine, on the neuroinflammatory associated brain dysfunctions. To achieve our aim, we used control rats or submitted rats to lipopolysaccharide (LPS) challenge. 30 min after LPS challenge, the animals received either saline, Eserine, JWH-133 or Eserine+JWH-133. After 24h, animals were submitted to the habituation to T maze, Rotarod and activity cage tests. The rats were killed after and were evaluated for central and peripheral inflammatory and oxidative parameters. We observed that the use of Eserine, JWH-133 or Eserine + JWH-133 reverted the increases in the inflammatory markers [interleukin 6 (IL6), vascular cell adhesion molecule 1(VCAM-1) and Eselectin] and oxidative-nitrous stress MDM, and that the anti-inflammatory, antioxidant properties of both JWH-133 and Eserine successfully improve the LPS induced brain dysfunction. The results observed in this study reinforce the role of microglia activation regulating agents, in particular, JWH-133 and Eserine, in the brain dysfunction associated with endotoxemia.

The effects of eserine and neostigmine on the guinea-pig ileum and on ileal longitudinal muscle strips.

Abstract Eserine and neostigmine produced spasms of the guinea-pig isolated ileum that were concentration-related (4 ng-16 μg/ml). Hexamethonium (100 μg/ml) and tetrodotoxin (100 ng/ml) reduced the spasmogenic activity of both drugs. Neostigmine, but not eserine, overcame the hexamethonium antagonism. Pretreatment of the ileum with dyflos (1 μg/ml for 10 min) did not affect the action of either eserine or neostigmine, therefore the spasm was not due to inhibition of cholinesterase. The residual response to eserine or neostigmine after tetrodotoxin was abolished by hyoscine (4 ng/ml). Isolated longitudinal muscle strips were so prepared to be innervated or denervated. Both types of strip gave similar bradykinin maxima but the response of the denervated strip to eserine and neostigmine was reduced to 40% of the innervated strip and the remaining response was blocked by hyoscine (2 ng/ml). It is concluded that eserine and neostigmine have an indirect action on the smooth muscle of the ileum that is the result of acetylcholine release from cholinergic nerves. Inhibition of cholinesterase would not seem to be important for this action. A second component of the action of these two drugs appears to be a direct effect on the muscarinic receptors of the smooth muscle.

Effect of eserine injected intraventricularly on behaviour and on activity of cholinesterase in some structures of the cerebral ventricles of the conscious cat.

Effect of eserine injected intraventricularly on behaviour and on activity of cholinesterase in some structures of the cerebral ventricles of the conscious cat.

Cell proliferation and tumor formation induced by eserine, an acetylcholinesterase inhibitor, in rat mammary gland

Environmental chemicals may be involved in the etiology of breast cancer. There is substantial evidence that breast cancer risk is associated with prolonged exposure to female hormones. Among these hormonal influences a leading role is attributed to the ovarian hormone estradiol, since breast cancer does not develop in the absence of ovaries. The rat mammary gland has special characteristics that make it an ideal organ for studying development, cell proliferation and transformation. In vivo and in vitro model systems for cell proliferation and mammary carcinogenesis have allowed morphological and biochemical analysis under different experimental conditions. The aim of this study was to examine the effect of eserine, an acetylcholinesterase inhibitor, as are the organophosphorous compounds malathion and parathion, and 17beta estradiol on cell proliferation and tumor formation that takes place in the rat mammary gland after in vivo and in vitro treatment. These studies showed that eserine and 17beta estradiol were capable of inducing carcinogenesis in the epithelium of rat mammary glands. It was found that there was a significant increase in the number of cells per duct of the 44-day-old rat mammary gland after the 10-day eserine treatment, compared to the control. A higher increase was observed in the animals treated for 10 days with eserine followed by 30-daily injections of estrogen in comparison to control animals. In 12 animals, two mammary tumors were directly developed in response to 17beta estradiol injected at 39 days of age with a latency period of 180 and 245 days, respectively. Such tumors were metastatic to the lung. These results suggest that terminal end buds are major targets related to rat mammary carcinogenesis and 17beta estradiol can be an initiator and promoter in this process.

Anticholinesterase effect of eserine (physostigmine) in fish and crustacean species

The kinetic characteristic (Km) of cholinesterase from the crab Chasmagnathus granulata, the shrimp Farfantepenaeus paulensis and the fish Odontesthes bonaeriensis were compared and correlated with the anticholinesterasic effect of eserine (physostigmine). For the crustaceans, the estimated Km values were about 5-8 times higher than that estimated for the fish (0.04 mM). In the crab and the shrimp, the concentration of eserine which inhibited 50% of cholinesterase activity (IC50) was estimated as 5.33x10-4 and 4.33x10-4 mM, respectively. In both cases, it was significantly higher (P < 0.05) than that estimated for the fish larvae (7.43x10-5 mM). A high Km could reflect a lower affinity of the cholinesterase for its natural substrate, acetylcholine, or for substrate analogues such as carbamates and organophosphorous pesticides. If we consider the IC50 for eserine as an index of enzyme susceptibility to pesticide inhibition, the cholinesterase from the fish larvae may be a better useful tool in assays for pesticide biomonitoring than that from crustacean species.

Eserine and other tertiary amine interactions with Torpedo acetylcholine receptor postsynaptic membrane vesicles.

Interaction of the tertiary amines, arecolone, eserine (physostigmine), (+)-epibatidine, and (+/-)-epibatidine, with Torpedo nicotinic acetylcholine receptor-enriched membrane vesicles was investigated to characterize their action on the receptor, using stopped-flow thallium (I)-flux spectrofluorimetry. Arecolone, (+)-epibatidine, and (+/-)-epibatidine were agonists with activation constants of 390, 19, and 39 microM, respectively. Eserine was not an agonist but rather an antagonist for agonist-induced activation of the receptor with an inhibition constant of approximately 150 microM. The choice of the fluorescent dye used (entrapped within the membrane vesicles) was critical for interpretation of the effects of eserine. With 1,3,6,8-pyrene tetrasulfate (PTS), eserine appeared to act as an agonist. However, it was shown that such an effect was caused by rapid diffusion of the uncharged form of the amine across the membrane followed by direct interaction with PTS rather than eserine-induced cation transport. The use of a different fluorescent dye, 8-aminonaphthaline-1,3,6-trisulfate, with which eserine does not interact allowed demonstration of the action of eserine as an antagonist rather than as an agonist.

Pontine reticular formation is involved in catalepsy produced by cholinergic drugs

Bilateral kainic acid lesions of the ventro-medial (VM) thalamic nucleus of rats which greatly reduced the catalepsy produced by haloperidol (2 mg/kg i.p.) not only did not reduce, but even enhanced, the cataleptogenic effect of eserine (1 mg/kg i.p.) and arecoline (30 mg/kg i.p.). This finding is in accord with former conclusions that catalepsy produced by cholinergic drugs does not depend on striatal mechanisms. In rats with kainic acid lesions of the VM thalamic nucleus, and similarly in intact, non-lesioned rats, systemic administration of eserine and arecoline potentiated the catalepsy produced by microinjections of carbachol (2 microg) into the pontine reticular formation (PRF). Atropine microinjected bilaterally into the PRF attenuated the cataleptogenic effect of eserine and arecoline i.p. We suggest that the PRF is a site at which systemically given cholinergic drugs act to produce catalepsy.

Modulation of the influences of cortical input on hippocampal neurons by cholinergic substances

The cholinergic modulation of responses of individual neurons and of the focal potentials of the hippocampus, induced by electrical stimulation of the perforant path or mossy fibers were studied in two groups of unanesthetized rabbits, one with an intact septal region (IS), and one with its basal undercutting (BU). In all of the animals the responses to stimulation were blocked or markedly suppressed in a substantial portion of the neurons (50% in IS, 69% in BU) against the background of the administration of eserine. Facilitation of the responses was observed in 10 and 8% of cases, respectively. Scopolamine restored the initial reactivity of hippocampal neurons and intensified responses to stimulation of the perforant path. The effect of eserine was reproduced by stimulation of the medial septal region (MS-DB). The depressive effect of stimulation of the MS-DB was intensified by the administration of eserine and blocked by scopolamine. Brief conditioning stimulation of the MS-DB which imitates a theta salvo facilitated responses to test stimulation of the MS-DB with delays of 70-150 msec, but suppressed them at smaller and greater intervals. Focal potentials in response to stimulation of the perforant path in CA1 were suppressed to an equal extent (by 43%) during sensory stimulation inducing natural theta rhythm, during the action of eserine, and with stimulation of the MS-DB In the BU group, these effects led to the complete suppression of focal potentials; scopolamine restored them. It is hypothesized that the principal function of the septohippocampal cholinergic input resided in the negative filtration of signals arriving against the background of theta rhythm that has been turned on by another, preceding influence, as a result of which their interference with the processing and recording of received information is prevented.

Synaptic interactions involving acetylcholine, glutamate, and GABA in rat auditory cortex.

Using electrophysiological techniques in the in vitro rat auditory cortex, we have examined how spontaneous acetylcholine (ACh) release modifies synaptic potentials mediated by glutamate and gamma-aminobutyric acid (GABA). Single stimulus pulses to lower layer VI elicited in layer III a four-component (A-D) extracellular field response involving synaptic potentials mediated by glutamate and GABA. The cholinesterases inhibitor eserine (10-20 microM) or the cholinergic agonist carbachol (25-50 microM) depressed by 10-50% the glutamatergic components A and C, and the GABAergic components B and D. Atropine reversed the depressive effects of eserine and carbachol. A novel finding was that the degree of depression of component A varied inversely with stimulus intensity. However, during partial pharmacological antagonism of GABAA receptors, depression of A varied directly, not inversely, with stimulus intensity. Normally, then, depression of A is offset by reduced GABAergic inhibition of A. We also tested for differential depression of responses mediated by N-methyl-D-aspartate (NMDA) versus non-NMDA glutamate receptors. Following physiological and pharmacological isolation of the responses, eserine depressed the non-NMDA, but not the NMDA, receptor-mediated potential. Since the isolated NMDA potential still could be depressed by carbachol, the data suggested that activation of NMDA receptors may reduce spontaneous ACh release. In support of this, preincubation of slices in NMDA (10-20 microM) largely prevented eserine's, but not carbachol's, depression of components A and B. These results permit three conclusions of relevance to cortical information processing: (1) spontaneous ACh release tonically depresses synaptic potentials mediated by glutamate and GABA; (2) ACh depresses responses to weak inputs to a greater degree than responses to strong inputs: (3) activation of NMDA receptors may "feedback" to reduce ACh release, a mechanism that could place regulation of local ACh release under glutamatergic afferent control.

Accumulation of 3H‐Phosphoinositides Mediated by Muscarinic Receptors in the Developing Chick Retina: Inhibition of Carbachol‐Induced Response by Glutamate Receptors

In the present work we show the development of carbachol-induced accumulation of 3H-inositol phosphates (3H-InsPs) in the chick embryonic retina and its regulation by glutamate receptors. Although basal levels of 3H-InsPs increased during development, the retinal response to carbachol was high in the early developing stages and decreased after synaptogenesis in the retina. Eserine also stimulated the turnover of phosphoinositides in the embryonic but not in the mature retina. The effect of eserine could be blocked by atropine, suggesting that acetylcholine could be released from developing retina cells and further stimulate the turnover of InsPs in the embryonic tissue. Our data also show that muscarinic stimulation of turnover of 3H-InsPs could be blocked by stimulation of glutamatergic ionotropic receptors. Moreover, the effect of glutamate agonists did not seem to be mediated by the release of other neurotransmitters such as GABA, glycine, adenosine, or dopamine from the tissue because these neurotransmitters did not interfere with the retinal response to carbachol. These results suggest that muscarinic activation of phosphoinositide turnover occurs mainly in the embryonic retina and that activation of glutamate receptors can inhibit directly the muscarinic stimulation of hydrolysis of 3H-InsPs in this tissue.

Melatonin deacetylase activity in the pineal gland and brain of the lizards anolis carolinensis and sceloporus jarrovi

Melatonin modulates a variety of rhythmic processes in vertebrates, and is synthesized in both the retina and pineal gland. We have shown previously that retinal melatonin is deacetylated generating 5-methoxytryptamine, which is then deaminated by monoamine oxidase, producing 5-methoxyindoleacetic acid and 5-methoxytryptophol. This process occurs within the eyes of a variety of vertebrates including the iguanid lizard Anolis carolinensis. To determine whether melatonin deacetylase activity also occurs in the pineal organ or in other parts of the lizard brain, pineals and brains of Anolis carolinensis and Sceloporus jarrovi were cultured in the presence of [ 3H-methoxy]-melatonin. High-performance liquid chromatography of the resulting culture media and tissues revealed the generation of radiolabeled 5-methoxytryptamine and 5-methoxyindoleacetic acid. These two methoxyindoles were the only radiolabeled metabolites detectable, and together accounted for all melatonin lost. Both the loss of melatonin and the production of melatonin metabolites were inhibited by inclusion of 100 μM eserine, an inhibitor of the melatonin deacetylase. Pargyline, a monoamine oxidase inhibitor, reduced the production of 5-methoxyindoleacetic acid and increased the production of 5-methoxytryptamine relative to control incubations. Similar effects of eserine and pargyline were seen in eyecup, brain and pineal gland, but the specific activity of melatonin deacetylation in cultured pineal glands was much greater than in either brains or eyecups. These results indicate that pineal glands of both Anolis carolinensis and Sceloporus jarrovi can rapidly catabolize melatonin by a mechanism very similar to that in the eye, that the melatonin deacetylation pathway exists elsewhere in the iguanid brain, and also extend our previous observations of ocular melatonin deacetylation to an additional species.

Potentiation and suppression by eserine of muscarinic synaptic transmission in the guinea‐pig hippocampal slice.

1. The effects of the anticholinesterase eserine on CA3 pyramidal cells and dentate gyrus granule cells in guinea-pig hippocampal slices were investigated with single-electrode current-clamp and voltage-clamp recording. 2. In the majority of cells superfused with eserine (0.5-10 microM) for 3-10 min, tetanic stimulation near the cell layers elicited a delayed depolarization (slow EPSP; duration up to 60 s) at a pre-stimulation membrane potential of -60 mV. The slow EPSP was blocked by atropine (1 microM). 3. Under voltage clamp at -60 mV holding potential, an apparent inward current (slow EPSC) with a similar time course to the slow EPSP was observed. 4. The amplitude of the delayed inward current was about 50 pA. The amplitude increased at holding potentials more positive than -60 mV. At holding potentials negative to -60 mV, the delayed inward current was too small to allow reliable analysis. In the absence of eserine, there was a delayed inward current, which was rather small, however, due to a superimposed outward current. 5. Eserine reduced the after-hyperpolarization following a train of action potentials. This effect was antagonized by atropine, but not to pirenzepine. In voltage-clamp recording, eserine reduced a current termed IAHP. 6. CA3 neurones treated with eserine exhibited a region of negative slope conductance (in tetrodotoxin). The slow inward current which developed at clamp potentials between -50 and -40 mV was reduced by Ni2+ (50 microM). The effect of eserine on slope conductance increased with time of exposure. In all neurones superfused with eserine for more than 60 min, burst discharges were observed. Burst discharges were blocked by atropine and Ni2+, but not by pirenzepine. 7. In cells superfused with eserine for more than 1 h, tetanic stimulation failed to elicit a slow EPSP or EPSC. Currents induced by focal acetylcholine (ACh) application were first enhanced by eserine, but blocked after exposure to eserine for more than 1 h. Blockade of ACh-induced currents was also observed after bath application of carbachol (CCh) in a concentration (0.2 microM) in which it did not induce an inward current at -60 mV holding potential. Further, the slow EPSP faded when elicited by repeated tetanic stimulation. 8. While the observed effects of eserine on hippocampal neurones can be explained by eserine's well-known ability to block acetylcholinesterase activity, our data indicate that the effects of eserine involve more than one muscarinic receptor site, i.e. desensitizing and non-desensitizing postsynaptic receptor sites.

Cholinergic regulation of female sexual behavior in rats demonstrated by manipulation of endogenous acetylcholine

Infusions of the cholinesterase inhibitor, eserine, into the lateral ventricle of the brain facilitated lordosis in ovariectomized, estrogen primed female rats. Lordosis was also facilitated by infusions of 5 or 10 μg acetylcholine when this was accompanied by a low dose of eserine. Systemic treatment with the muscarinic antagonist, atropine (2 mg), completely blocked the facilitative effects of eserine and acetylcholine. In female rats made highly receptive by treatment with estrogen and progesterone, lordosis was inhibited by infusion of scopolamine into the lateral ventricles. These results agree with previous findings that sexual receptivity is regulated in part by endogenous cholinergic activity.

Evidence that cholinergic axon terminals are equipped with both muscarinic and adenosine receptors

The release of 3H-acetylcholine (ACh) from longitudinal muscle strips of guinea pig ileum, which were previously incubated with 3H-choline, was measured by scintillation spectrometry. The release of ACh evoked by electrical field stimulation was inhibited in the following ways: stimulating muscarinic receptors directly with oxotremorine or indirectly with eserine by increasing ACh concentration in the surrounding axon terminals or stimulating adenosine receptors by increasing the biophase concentration of adenosine with dipyridamole. The muscarinic antagonist atropine and the adenosine receptor antagonist theophylline enhanced ACh release. Atropine prevented the effect of eserine and oxotremorine on ACh release and theophylline counteracted the effect of dipyridamole. When the release of ACh was under the inhibitory effect ofmuscarininc receptor stimulation theophylline did not increase ACh release. Under these conditions atropine caused an extremely high increase in the release of ACh, which was not further enhanced by theophylline. When the extracellular level of adenosine was increased by dipyridamole, eserine, atropine or eserine and atropine together, they were unable to change the release of ACh, while theophylline increased release of ACh. Therefore, it is concluded that the muscarinic receptor mediated inhibition of ACh release is not due to previously released adenosine. Thus, adenosine and muscarinic feedback systems seem to be independent and each cholinergic nerve ending contains both adenosine and muscarinic receptors.

Responses of phasic and tonic hippocampal theta-on cells to cholinergics: differential effects of muscarinic and nicotinic activation

The discharge patterns of tonic and phasic hippocampal formation theta-on cells were recorded in response to systemic administration of cholinergic agents, in urethane-anesthetized rats. Eserine and carbachol resulted in long trains of slow-wave theta and accompanying activation of tonic and phasic theta-on cells. Both slow-wave theta and the characteristic accompanying discharge patterns of theta-on cells were blocked by administration of atropine SO 4, providing evidence that the effects of eserine and carbachol were mediated by muscarinic receptors. The systemic administration of nicotine resulted in 20–30 s of slow-wave theta and during this time, both tonic and phasic theta-on cell discharges were suppressed.

Facilitation and inhibition of nicotinic transmission by eserine in the sympathetic ganglia of the rabbit

The effects of eserine on neurons and on ganglionic transmission of the isolated superior cervical ganglia of the rabbit were investigated by means of intracellular recording techniques. At the concentration of 10μM or less, eserine reversibly increased the amplitude and duration of the fast excitatory postsynaptic potential (f-epsp) induced by preganglionic nerve stimulation and of the membrane depolarization evoked by iontophorcetically-applied acetylcholine (ACh), but not carbachol. At the concentration of 50 μM or more, eserine consistently and reversibly depressed the fast excitatory postsynaptic potential as well as the depolarization induced by iontophoretic application of either ACh or carbachol. Furthermore, depolarization by ACh evoked in a low Ca/high Mg solution, which blocked the liberation of transmitter was similarly reduced by eserine in greater concentrations. The passive membrane properties of the sympathetic neurons were not significantly altered by eserine in the majority of neurons studied. The results indicate that the facilitatory action of eserine on ganglionic transmission may be explained by its anticholinesterase activity, whereas eserine-induced block of transmission appears to be related to a direct interaction between the compound and the postsynaptic ACh receptor-channel complex.

Histamine H2-receptor agonists and antagonists on pancreatic exocrine secretion of the dog.

The use of H2-receptor agonists and antagonists allowed us to establish that histamine H2-receptors are present in pancreatic exocrine tissue and their stimulation caused a dose-dependent increase in pancreatic juice. The fact that H2-antagonists from one side and aminoguanidine from the other were unable to modify basal levels of pancreatic secretion, seems to minimize a role for H2-receptors in the regulation of pancreatic secretion. On the other hand H2-antagonists modified ceruletide-induced secretion in different ways according to the different molecules. Ranitidine strongly potentiated whereas cimetidine, oxmetidine and mifentidine slightly inhibited the effect of ceruletide. The stimulatory effect of eserine and the inhibitory effect of atropine indicate a cholinergic interference in the action of ceruletide. Therefore the potentiating effect of ranitidine may be related to its cholinomimetic action and the inhibitory effect of the other H2-antagonists may be connected with an anticholinergic effect. However, the potentiating effect of aminoguanidine on ceruletide-induced secretion may indicate a possible role for histamine in the response to ceruletide.

Activation of the cholinergic system and growth hormone release in the dog: functional interactions with other neurotransmitters.

In unanaesthetized dogs iv administration of the cholinesterase inhibitor eserine (0.5 mg) induced a clear-cut rise in plasma canine growth hormone (cGH) levels. Diphenhydramine and meclastine, two antagonists of histamine (H) H1 receptors completely suppressed the GH-releasing effect of eserine, while cimetidine, an H2 receptor antagonist, only blunted and delayed it. Two long-lasting serotonin (5-HT) receptor antagonists, metergoline and pizotifen, partially or completely suppressed, respectively, GH release evoked by eserine, whereas fenfluramine, a releaser of neuronal stores of 5-HT and hence a functional activator of 5-HT neurotransmission, was ineffective in this context. Pimozide, a long-acting dopamine receptor antagonist, abolished the effect of eserine, whereas domperidone, which has the same pharmacological properties but does not cross the blood brain barrier, failed to do so. Finally, phentolamine, an antagonist of alpha-adrenoceptors, and propranolol, a beta-adrenergic antagonist, were completely ineffective in preventing the rise in plasma cGH levels induced by eserine, as was naloxone, an antagonist of opiate receptors. All these data demonstrate that, although cholinergic mechanisms are involved in the mechanism(s) underlying cGH release, the final common pathway for GH secretion is not cholinergic. Preservation of dopaminergic and H1 neurotransmission, probably within the blood barrier, is needed to allow the neuroendocrine transduction of cholinergic inputs, whereas the role of 5-HT neurotransmission remains uncertain.

Impact of methyl parathion toxicity and eserine inhibition on acetylcholinesterase activity in tissues of the teleost ( Tilapia mossambica) — a correlative study

Acetylcholinesterase (AChE) activity and acetylcholine (ACh) content of muscle, gill, liver and brain tissues of control and methyl parathion-exposed (MPE) fish were determined. In addition, in vitro concentrations of eserine necessary to produce inhibition of AChE equivalent to in vivo inhibition by sublethal amounts of methyl parathion (MP) were also investigated. AChE activity decreased in all tissues, while ACh content showed a corresponding increase. These observations indicate disruption of nerve impulse conduction. The in vitro effect of eserine on AChE activity differed with the type of MP action. These results are discussed in relation to the sensitivity and extent of innervation of various tissues.