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J T Coyle

Publications and source records attributed to J T Coyle.

At least 217 records · Page 12Linked to original sources
PubMed1985

Excitatory amino acid analogs evoke release of endogenous amino acids and acetyl choline from chick retina in vitro.

There is mounting evidence that excitatory amino acids may play a role in retinal synaptic neurotransmission. In this study, we demonstrate the release of endogenous amino acids and acetylcholine from isolated chick retina in vitro evoked by three excitatory amino acid analogs, kainic acid (KA), quisqualic acid (Quis), and N-methyl-D,L-aspartic acid (NMDA). The release is dose-dependent and involves putative transmitters from both inner and outer retina. Release from the inner retina is partially Ca2+-dependent, while release from the outer retina is Ca2+-independent and Na+-dependent. Release experiments carried out in the presence of specific excitatory amino acid blocking agents suggest that the release is mediated by two receptors, the kainate receptor and the NMDA receptor. These results are supportive of a role for excitatory amino acids in synaptic neurotransmission in both inner and outer retina.

Acetylcholine↗
PubMed1985

Method for the quantitation and characterization of the cholinergic neurotoxin, monoethylcholine mustard aziridinium ion (AF64A).

Monoethylcholine aziridinium ion (AF64A), which is generated from the precursor, acetylcholine mustard hydrochloride, exerts selective neurotoxic effects against brain cholinergic neurons when injected intracerebrally. Conditions associated with optimal generation of AF64A were examined. The results indicate that hydrolysis and cyclization of the precursor are optimal at 25 degrees C with the former occurring at pH 9.0 and the latter at pH 7.3. The aziridinium ion is best stabilized at pH 7.3 at 4 degrees C.

Aziridines↗
PubMed1985

N-Acetylaspartylglutamate: possible role as the neurotransmitter of the lateral olfactory tract.

N-Acetylaspartylglutamate, an endogenous brain peptide that binds with high affinity to a subpopulation of glutamate-binding sites in rat brain, is excitatory on rat piriform cortex pyramidal cells studied in a perfused brain slice. Both the monosynaptic excitation of the pyramidal cells elicited by stimulation of the lateral olfactory tract and the response to N-acetylaspartylglutamate were blocked by DL-2-amino-4-phosphonobutyrate but not by other excitatory amino acid antagonists. Responses to glutamate and aspartate, previously considered to be candidates as the lateral olfactory tract transmitter, were unaffected by 2-amino-4-phosphonobutyrate. Three days after unilateral bulbectomy there was a significant decrease in concentrations of N-acetylaspartylglutamate as well as aspartate, N-acetylaspartate, and gamma-aminobutyrate in the pyriform cortex of the side from which the olfactory bulb had been removed. These results are consistent with the possibility that N-acetylaspartylglutamate is the endogenous transmitter of the lateral olfactory tract.

Animals↗
PubMed1985

AF64A: an active site directed irreversible inhibitor of choline acetyltransferase.

Ethylcholine mustard aziridinium ion (AF64A, MEChMAz) has been proposed as a cholinergic neuron-specific neurotoxin. We report that in further studies on its mechanism of action incubation of the cholinergic neuroblastoma X glioma cell line, NG-108-15, with 100 microM AF64A resulted in a rapid decrease in cellular choline acetyltransferase (ChAT) activity which preceded cytotoxicity. Thus, a 60-85% decrease in ChAT activity was measured within 5 h of AF64A exposure, whereas cell lysis (measured as the release of the cytosolic enzyme lactate dehydrogenase into the medium) did not become apparent until 18 h of AF64A exposure. This led us to examine the effects of AF64A on partially purified ChAT. We report a concentration- and time-dependent inhibition of partially purified ChAT by AF64A that could not be reversed by dialysis but could be prevented by coincubation of the enzyme and AF64A with choline but not with acetyl-coenzyme A. We present kinetic evidence that choline and AF64A compete for the same site on the enzyme. In addition, thiosulfate, which inactivates the aziridinium ion, eliminated AF64A's capacity to inhibit the enzyme. AF64A also irreversibly inhibited partially purified choline kinase and acetylcholinesterase but not lactate dehydrogenase, alcohol dehydrogenase, carboxypeptidase A, or chymotrypsinogen, enzymes that do not use choline as a substrate or product. Thus, the data suggest that AF64A acts as an irreversible active site directed inhibitor of ChAT and possibly other enzymes recognizing choline.

Animals↗
PubMed1985

RBC choline and renal disorders during lithium treatment.

The authors measured RBC choline level, plasma choline level, and renal concentrating ability in 26 lithium-treated patients, seven psychiatric control subjects, and seven normal control subjects. An analysis of variance revealed no significant relationship between renal concentrating ability and either RBC choline level or RBC/plasma choline ratio.

Adult↗
PubMed1985

The characterization of the specific binding of [3H]-N-acetylaspartylglutamate to rat brain membranes.

[3H]-N-Acetylaspartylglutamate (NAAG) bound saturably and reversibly to crude synaptosomal rat brain membranes. Optimal binding occurred in Tris-HCl buffer, pH 7.2, at 37 degrees C using previously frozen, preincubated membranes. Saturation experiments revealed an apparent KD of 383 +/- 33 nM and a Bmax of 31 +/- 2 pmol/mg of protein. [3H]NAAG specific binding was displaceable by serine-o-sulfate, quisqualate, ibotenate, and glutamate with K1's in the nanomolar range, whereas the amino-phosphono analogues displaced [3H] NAAG in the micromolar range (APB greater than APV greater than APH). No specific binding was found in peripheral tissues. Within the central nervous system, the thalamus exhibited the greatest amount of binding, whereas binding was lowest in cortex. Calcium ions enhanced the specific binding, whereas sodium ions caused a concentration-dependent inhibition. These results suggest that [3H]NAAG labels an acidic amino acid receptor site designated "A-4," which recognizes the antagonist, 2-amino-4-phosphonobutyric acid, and that this receptor may mediate the neurophysiologic effects of endogenous NAAG.

Animals↗
PubMed1985

Dissociation between the excitatory and "excitotoxic" effects of quinolinic acid analogs on the striatal cholinergic interneuron.

Analogs of quinolinic acid were tested for excitatory properties in evoking neurotransmitter release from striatal cholinergic interneurons and for their ability to lesion these same neurons in vivo (excitotoxin activity). The ability of these analogs to inhibit the specific binding of several ligands thought to label excitatory amino acid receptors was also investigated. Dipicolinic acid (2,6-pyridine dicarboxylic acid) was found to be as potent and as efficacious as quinolinic acid (2,3-pyridine dicarboxylic acid) at N-methyl-D-aspartate (NMDA)-type receptors mediating [3H]acetylcholine release from striatal slices. However, unlike quinolinate, the structure of NMDA is not superimposable upon that of dipicolinic acid. Moreover, unlike quinolinic acid, dipicolinic acid injected intrastriatally did not produce detectable excitotoxic lesions. Most unexpectedly, phthalic acid (1,2-benzene dicarboxylic acid), which lacks a nitrogen, also evoked [3H]acetylcholine release from striatal slices, apparently by acting at NMDA-type receptors. Phthalic acid was equipotent to quinolinic acid and dipicolinic acid but possessed less intrinsic activity than these compounds in evoking [3H]acetylcholine release. Despite its lack of a nitrogen and low intrinsic activity, intrastriatal injection of phthalic acid produced axon-sparing lesions of intrinsic cell bodies, like quinolinic acid as assessed by neurochemical and histologic methods. Quinolinic acid, dipicolinic acid and phthalic acid were moderately potent inhibitors (Kl = approximately equal to 100 microM) of the specific binding of 2-[3H]amino-7-phosphonoheptanoic acid a compound thought to be a competitive antagonist of NMDA-type receptors. In contrast, these three compounds failed to inhibit the chloride-dependent or chloride-independent binding of L-[3H]glutamate or [3H]kainic acid. The present results suggest a major dissociation between the structure-activity relationships for "excitotoxicity" vis-à-vis excitation as reflected in the [3H]acetylcholine release model, for compounds acting at NMDA-type receptors.

Animals↗
PubMed1985

Effective management with lithium of a persistent, post-traumatic hypomania in a 10-year-old child.

A 10-year-old child who suffered closed head trauma resulting in a coma of 1 week's duration at the age of 4, developed a persistent, severe behavioral disorder characterized by hyperactivity, impulsivity, distractability, irritability, and grandiosity. Prior attempts at treatment with stimulants and behavioral modification were unsuccessful. Treatment with lithium carbonate resulted in a marked reduction in symptoms and attenuation in her emotional lability.

Bipolar Disorder↗
PubMed1985

Lesions in nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments.

The functional contribution of nucleus basalis magnocellularis (NBM) and the medial septal area (MSA) to memory was evaluated in two different spatial discriminations. Preoperatively, rats were trained to a criterion level of performance in a simultaneous left/right discrimination on the stem of a T-maze (a trial-independent memory) and a discrete-trial, rewarded alternation discrimination on the arms of the T-maze (a trial-dependent memory). Bilateral lesions were made by injecting ibotenic acid (IBO) into the NBM, MSA, both NBM and MSA, or dorsal globus pallidus (DGP), and by radiofrequency current (RF) in the NBM and MSA. Control rats received operations in which either no current was passed or no neurotoxin was injected. Lesions in the NBM, MSA, or both the NBM and MSA produced a similar pattern of behavioral changes relative to the performance of controls; postoperative reacquisition of the arm discrimination was initially impaired but showed recovery to normal levels, whereas postoperative reacquisition and reversal of the stem discrimination was not impaired (except following the combined NBM and MSA lesion). Lesions of the DGP had no effect on choice accuracy in any discrimination. When the discrimination on the arms was made more difficult by increasing the delay interval during which the information had to be remembered, rats with combined NBM and MSA lesions were again impaired relative to controls and showed no signs of recovery of function. These results provide information about the behavioral functions of the basal forebrain cholinergic system and suggest that pathological changes in certain components of this system can cause disorders of memory.

Animals↗
PubMed1984

Characterization of a glutamic acid neurotransmitter binding site on neuroblastoma hybrid cells.

Glutamate is thought to be a major excitatory neurotransmitter in the central nervous system. To study the glutamate receptor and its regulation under carefully controlled conditions, the specific binding of [3H]glutamate was characterized in washed membranes isolated from a neuroblastoma X retina hybrid cell line, N18-RE-105. [3H]Glutamate bound in a saturable and reversible fashion with an apparent dissociation constant, KD, of 650 nM and a maximum binding capacity, Bmax, of 16 pmol/mg of protein. Pharmacologic characterization of the site indicates that it closely resembles the Na+-independent binding site for glutamate found on brain membranes and thought to be an excitatory amino acid neurotransmitter receptor. Thus, while kainate, N-methyl-DL-aspartate, and nonamino acid ligands did not displace [3H]glutamate, quisqualate and ibotenate were potent inhibitors of specific binding. Furthermore, this binding site is regulated by ions in a manner which resembles that described in the hippocampus (Baudry, M., and Lynch, G. (1979) Nature (Lond.) 282, 748-750). Calcium (10 mM) increased the number of binding sites 2.6-fold with no change in receptor-ligand affinity. Lanthanum (1 mM) was the only other cation added which enhanced (3-fold) the binding of [3H]glutamate. Monovalent cations resulted in a decrease in the number of glutamate binding sites. Incubation of membranes in the presence of chloride ions caused a marked increased in [3H] glutamate binding, an effect which was synergistic with that of calcium incubation. Thus, N18-RE-105 cells possess a binding site for [3H]glutamate pharmacologically similar to an excitatory neurotransmitter binding site in brain and which exhibits regulatory properties resembling those previously described in hippocampal membranes, providing an excellent model for mechanistic studies.

Animals↗
PubMed1984

Agonists and cations regulate the glutamic acid receptors on intact neuroblastoma hybrid cells.

Glutamate is thought to be a major excitatory neurotransmitter in the vertebrate brain. In the preceding paper (Malouf, A. T., Schnaar, R. L., and Coyle, J. T. (1984) J. Biol. Chem. 259, 12756-12762), we demonstrated specific binding of [3H]glutamate to membranes from a neuroblastoma hybrid cell line, N18-RE-105. These sites are pharmacologically and kinetically similar to those seen on rat brain membranes and are regulated by ions added to the isolated membranes. In the current paper, we describe an additional level of regulation for the glutamate receptor in this cell line. Long-term incubation (72 h) of intact N18-RE-105 cells with glutamate (10 mM) results in a 2- to 3-fold increase in [3H]glutamate binding. Scatchard analysis reveals that the increase in binding is due to an increase in the number of glutamate receptors without significant change in their affinity. The ability of glutamate analogs to induce such up-regulation mirrors their ability to compete for [3H]glutamate binding to isolated membranes, suggesting that up-regulation is receptor-mediated. Binding of [3H]glutamate to membranes isolated from cells grown in the presence of glutamate can be further up-regulated by brief exposure (10 min) of the isolated membranes to calcium ions. This suggests that agonist-induced and calcium-induced up-regulation occur via independent mechanisms. The short-term ion-induced up-regulation and the long-term agonist-induced up-regulation described in this paper may model two levels of synaptic potentiation reported to occur in the vertebrate hippocampus. The N18-RE-105 cell line may offer a homogeneous cell type in which to study the molecular mechanisms underlying these phenomena.

Amino Acids↗
PubMed1984

Evidence for the existence of putative dopamine-, adrenaline- and noradrenaline-containing vagal motor neurons in the brainstem of the rat.

A combined technique utilizing retrograde transport of horseradish peroxidase (HRP) combined with immunocytochemistry using antibodies raised against tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyl transferase (PNMT) has been used to characterize monoaminergic neurons located within the region of the brainstem vagal motor nucleus. TH-immunoreactive (IR) but not DBH-IR and PNMT-IR neurons were double labelled predominantly at the caudal-most pole of the dorsal motor nucleus of the vagus (dmnX), whereas double-labelled PMNT and DBH plus TH-IR neurons extended from levels just rostral to the obex to 1-2 mm rostrally in the medial and lateral poles of the dmnX, respectively. The presence of putative dopamine (DA), noradrenaline (NA) and adrenaline (A) neurons in topographically distinct regions of the dmnX implicates, DA, NA and A in the modulation of cholinergic transmission at the level of parasympathetic ganglia in discrete parts of the thoracic and abdominal viscera.

Animals↗
PubMed1984

Effects of intrastriatal injections of the cholinergic neurotoxin AF64A on spontaneous nocturnal locomotor behavior in the rat.

Rats with bilateral striatal cholinergic lesions induced by the neurotoxin AF64A were found to have increased spontaneous nocturnal locomotor activity as measured in terms of the amount of time spent moving, the total distance traveled and the number of episodes and time of stereotypic behaviors. No significant differences between control and AF64A injected rats were found in the actual velocities between the two groups indicating that the rats were simply spending more time moving rather than moving with greater speed. Striatal activity of choline acetyltransferase (CAT) was significantly decreased in AF64A treated rats compared to controls, whereas the activities of glutamate decarboxylase (GAD) were not. Furthermore, there were no significant differences between groups in enzymatic activities of CAT and GAD in either the cortex or the hippocampus, indicating that the lesion was restricted to the striatum. The hyperactivity found in these rats after intrastriatal injection of AF64A supports a role for the striatal cholinergic system in locomotor behavior.

Acetylcholine↗
PubMed1984

Glutamate-containing dipeptides enhance specific binding at glutamate receptors and inhibit specific binding at kainate receptors in rat brain.

The dipeptide, L-phenylalanyl-L-glutamate (PG), augments the specific binding of the excitatory amino acid receptor antagonist, [3H]2-amino-7-phosphonoheptanoic acid (APH), to rat forebrain membranes by 5-fold at 100 microM with an EC50 of 4.9 microM. The increase in the specific binding of [3H]AHP induced by PG results exclusively from an increase in Bmax. In contrast, PG inhibits the specific binding of [3H]kainic acid to forebrain membranes with a Ki of 6.8 microM. Of several related peptides examined, active ones affected the two receptor sites in a reciprocal fashion. The results suggest an allosteric interaction between [3H]APH and kainate receptors modulated by glutamate-containing peptides.

2-Amino-5-phosphonovalerate↗