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J H Connick

Publications and source records attributed to J H Connick.

25 records · Page 2Linked to original sources
PubMed1988

Excitatory amino acid antagonists and endogenous aspartate and glutamate release from rat hippocampal slices.

1. The effect of excitatory amino acid agonists and antagonists on the efflux of endogenous aspartate and glutamate from the rat hippocampus in vitro was studied. 2. None of the compounds tested had any effect on the basal efflux of endogenous aspartate and glutamate. 3. 2-Amino-5-phosphonovaleric acid (APV), 2-amino-7-phosphonoheptanoic acid (APH) and MK-801 all reduced the potassium-evoked efflux of aspartate and glutamate by between 14.9% and 34.3% (P less than 0.05). 4. The depression of efflux brought about by APV was still observed in the presence of tetrodotoxin. 5. Neither N-methyl-D,L-aspartate nor quinolinic acid had any effect on the potassium-evoked efflux of aspartate and glutamate. 6. These results imply the existence of presynaptic amino acid receptors that are capable of modulating the efflux of endogenous aspartate and glutamate.

2-Amino-5-phosphonovalerate↗
PubMed1988

Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo.

1. The effect of quinolinic acid, N-methyl-D,L-aspartate (NMDLA) and kainate on the release of endogenous and exogenous amino acids from the rat cerebral cortex in vitro and in vivo was studied. 2. Neither quinolinic acid nor NMDLA had any effect on the basal or potassium-evoked release of [3H]-D-aspartate from slices of rat cerebral cortex either in the presence or absence of magnesium. Kainic acid failed to modify the basal efflux of [3H]-D-aspartate but significantly inhibited (by 34.4% +/- 0.04%, P less than 0.05) the potassium-evoked release. 3. Neither quinolinate nor NMDLA had any effect on the basal efflux of endogenous amino acids from rat cortical slices either in the presence or absence of magnesium ions at concentrations between 10 microM and 5 mM. 4. Both NMDLA (1 mM) and quinolinate (5 mM) produced an efflux of endogenous aspartate (371.4% +/- 11.6%; 389.3% +/- 12.1%) and glutamate (405.4% +/- 13.6%; 430.1 +/- 8.7%) respectively from the rat cerebral cortex in vivo (P less than 0.01). The quinolinic acid-evoked efflux was abolished by the NMDLA antagonist, 2-amino-5-phosphonovaleric acid (200 microM). 5. Kainic acid also caused an efflux of endogenous amino acids from the rat cerebral cortex in vivo. However, the profile of this release was different from that produced by quinolinate and NMDLA. 6. The results add further support to the suggestion that quinolinic acid acts at the NMDLA-preferring receptor and may also explain the requirement for intact afferent projections for the neurotoxic effects of quinolinate to be manifested.

2-Amino-5-phosphonovalerate↗
PubMed1987

Endogenous excitotoxic agents.

Although glutamate and aspartate are among the most likely compounds to function as central neurotransmitters, and both can produce cell death in neonatal animals, the efficient uptake systems for these amino acids mean that exceptionally high concentrations are required for toxicity in adults. A better candidate for an endogenous neurotoxin is quinolinic acid, which produces cell death via activation of the N-methyl-aspartate receptors. Several differences of detail between the activity of quinolinate and N-methyl-aspartate may indicate the existence of subpopulations of the N-methyl-aspartate receptor. Another compound in the same 'kynurenine' pathway as quinolinate, kynurenic acid, is an antagonist of the excitatory and neurotoxic actions of quinolinate, and the overall excitability of the central nervous system and the occurrence of cell death may therefore result from a balance between the concentrations of quinolinate and kynurenate.

Animals↗
PubMed1986

The effect of kainic, quinolinic and beta-kainic acids on the release of endogenous amino acids from rat brain slices.

It has been suggested that the neurotoxic properties of quinolinic acid and kainic acid may, at least in part, involve an indirect action on nerve terminals containing glutamate. In the present study it is confirmed that kainate causes the release of endogenous glutamate from rat hippocampal slices, but that quinolinic acid does not share this activity. In addition beta-kainic acid was found to depress the potassium evoked release of endogenous glutamate at relatively high concentrations and this effect may underlie the anticonvulsant properties of this substance.

Amino Acids↗
PubMed1986

O-phosphohomoserine, a naturally occurring analogue of phosphonate amino acid antagonists, is an N-methyl-D-aspartate (NMDA) antagonist in rat hippocampus.

O-Phosphohomoserine, an analogue of the excitatory amino acid antagonist 2-amino-phosphonovalerate, has been synthesized and tested for activity as an excitatory amino acid antagonist. The tests were carried out on 500 micron thick slices of rat hippocampus superfused in vitro at 30 degrees C. Antidromic and orthodromic potentials were studied in the CA1 region, recording from the pyramidal cell layer. At concentrations of 0.5 and 1 mM the compound produced a weak but significant antagonism of the depression of evoked potentials produced by N-methyl-D-aspartate with no effect on the responses produced by kainic or quisqualic acids. O-Phosphohomoserine was not metabolised by brain homogenates or by alkaline phosphatases. Since O-phosphohomoserine is known to occur naturally in lower organisms, it would be of interest to seek its existence in the animal nervous system.

Animals↗
PubMed1985

The role of kynurenines in diabetes mellitus.

Although different forms of diabetes are known to exist, there are a number of factors which occur in these states all of which would contribute to an increase in the synthesis of the kynurenine metabolites of tryptophan, xanthurenic acid in particular. Conditions giving rise to increased kynurenine metabolism include pregnancy, oral contraceptives, emotional and metabolic stress. We propose a mechanism by which kynurenines act to reduce the concentration of active insulin in plasma and thus give rise to a diabetic state.

Diabetes Mellitus↗