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A Grieve

Publications and source records attributed to A Grieve.

32 records · Page 2Linked to original sources
PubMed1991

Stimulation of gamma-[3H]aminobutyric acid release from cultured mouse cerebral cortex neurons by sulphur-containing excitatory amino acid transmitter candidates: receptor activation mediates two distinct mechanisms of release.

In primary cultures of mouse cerebral cortex neurons, sulphur-containing excitatory amino acids (SAAs; namely, L-cysteine sulphinate, L-cysteate, L-homocysteine sulphinate, L-homocysteate, S-sulphocysteine) at concentrations ranging from 0.1 microM to 1 mM evoked a saturable release of gamma-[3H]aminobutyric acid ([3H]GABA) in the absence of any other depolarizing agent. All SAAs exhibited essentially similar potency (EC50, 100-150 microM) in releasing [3H]GABA although a variable profile of maximal stimulatory effect was observed when compared with basal release. The intracellular accumulation of the lipophilic cation, [3H]tetraphenylphosphonium, was significantly reduced in the presence of all SAAs, thus verifying a depolarization of the neuronal plasma membrane. SAA-stimulated release of [3H]GABA was shown to comprise two distinct components, calcium-dependent and calcium-independent, which occur after activation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Thus, all SAA-evoked responses were antagonized by the selective, competitive NMDA-receptor antagonist, 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (IC50 range, greater than 50 microM) and the non-NMDA-receptor antagonist, 6,7-dinitroquinoxalinedione (IC50 range, 5-50 microM). Removal of magnesium ions from the superfusion medium caused a significant potentiation of SAA-evoked responses without having any effect on basal levels of [3H]GABA efflux, a result consistent with an involvement of NMDA-receptor activation. Calcium-independent release (i.e., that release remaining in the presence of 1 mM cobalt ions) was a distinct component but of smaller magnitude. Using 500 microM excitatory amino acid agonist concentrations, this component of release was (1) markedly attenuated by 15 microM SKF-89976-A, a non-transportable inhibitor of the GABA carrier, and (2) abolished when choline ions replaced sodium ions in the superfusion medium or when in the presence of excitatory amino acid receptor antagonists. These observations are clearly consistent with a receptor-mediated, depolarization-induced reversal of the GABA carrier.

Amino Acids↗
PubMed1989

Inhibition by excitatory sulphur amino acids of the high-affinity L-glutamate transporter in synaptosomes and in primary cultures of cortical astrocytes and cerebellar neurons.

A detailed kinetic study of the inhibitory effects of L- and D-enantiomers of cysteate, cysteine sulphinate, homocysteine sulphinate, homocysteate, and S-sulpho-cysteine on the neuronal, astroglial and synaptosomal high-affinity glutamate transport system was undertaken. D-[3H] Aspartate was used as the transport substrate. Kinetic characterisation of uptake in the absence of sulphur compounds confirmed the high-affinity nature of the transport systems, the Michaelis constant (Km) for D-aspartate uptake being 6 microM, 21 microM and 84 microM, respectively, in rat brain cortical synaptosomes and primary cultures of mouse cerebellar granule cells and cortical astrocytes. In those cases where significant effects could be demonstrated, the nature of the inhibition was competitive irrespective of the neuronal versus glial systems. The rank order of inhibition was essentially similar in synaptosomes, neurons and astrocytes. Potent inhibition (Ki approximately Km) of transport in each system was exhibited by L-cysteate, and L- and D-cysteine sulphinate whereas substantially weaker inhibitory effects (Ki greater than 10-1000 times the appropriate Km value) were exhibited by the remaining sulphur amino acids. In general, inhibition: (i) was markedly stereospecific in favor of the L-enantiomers (except for cysteine sulphinate) and (ii) was found to decrease with increasing chain length. Computer-assisted molecular modelling studies, in which volume contour maps of the sulphur compounds were superimposed on those of D-aspartate and L-glutamate, demonstrated an order of inhibitory potency which was, qualitatively, in agreement with that obtained quantitatively by in vitro kinetic studies.

Amino Acids↗
PubMed1989

Excitatory sulphur amino acid-evoked neurotransmitter release from rat brain synaptosome fractions.

The neuroactive sulphur-containing amino acids L-cysteate (CA), L-cysteine sulphinate (CSA), L-homocysteine sulphinate (HSA), S-sulpho-L-cysteine (SC) and L-homocysteate (HCA) evoked the release of previously accumulated D-[3H]aspartate from rat brain cerebrocortical and cerebellar synaptosome fractions in a manner that was wholly Ca2+-independent. However, analysis of endogenous release by hplc revealed the presence of both Ca2+-dependent and -independent component of L-glutamate release but only a Ca2+-independent component of L-aspartate release. CA, CSA, HSA and SC but not HCA evoked the release of previously accumulated [3H]GABA from synaptosome fractions by a mechanism shown to comprise both a Ca2+-dependent and -independent component. The specific antagonists of the N-methyl-D-aspartate (NMDA) receptor, 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-l-phosphonic acid (CPP) and the relatively selective competitive quisqualate (QUIS)/kainate (KA) receptor antagonist, 6-cyano-7-dinitroquinoxalinedione (CNQX), were ineffective in blocking the excitatory sulphur amino acid-evoked release of either D-[3H]aspartate, [3H]GABA or of endogenous established transmitter amino acids.

Amino Acids↗
PubMed1989

Neuroactive sulphur amino acids evoke a calcium-dependent transmitter release from cultured neurones that is sensitive to excitatory amino acid receptor antagonists.

A dose-dependent, saturable, and calcium-dependent release of gamma-[3H]aminobutyrate [( 3H]GABA) from cortical neurones and D-[3H]aspartate from cerebellar granule cells following stimulation by a range of L-enantiomers of neuroactive acidic sulphur amino acids has been demonstrated. Moreover, the sulphur amino acid-evoked release of the transmitter amino acids was found to be sensitive to the presence of both selective N-methyl-D-aspartate and quisqualate/kainate receptor antagonists. Following the recent demonstration of an endogenous location for several of the acidic sulphur amino acids and their excitotoxic involvement in several neuropathological states and coupled with the knowledge that many important CNS connections are still undefined as far as their excitatory transmitter or transmitters are concerned, the present findings are of immediate importance in the continued search for endogenous excitatory amino acid agonists in addition to glutamate and aspartate.

Amino Acids↗
PubMed1986

Differential changes in the content of amino acid neurotransmitters in discrete regions of the rat brain prior to the onset and during the course of homocysteine-induced seizures.

Changes in amino acid concentrations were investigated in selected regions of rat brain prior to the onset and during the course of epileptiform seizures induced by L-homocysteine. The concentration of gamma-aminobutyric acid (GABA) decreased preictally in substantia nigra (-18%), caudate putamen (-26%), and inferior colliculus (-46%). After seizure onset, the GABA content was further reduced in substantia nigra (-31%) and additionally in hippocampus (-18%). Preictal taurine levels were elevated in globus pallidus (+26%) and caudate putamen (+13%) but returned to normal after seizure onset. However, in hippocampus, taurine decreased both preictally (-22%) and after seizure onset (-56%). Glycine was reduced preictally only in globus pallidus (-13%). After seizure onset the direction of its concentration change varied in the brain regions studied. Glutamate levels decreased preictally in hippocampus (-10%) and hypothalamus (-46%) but increased in globus pallidus (+14%). Normal levels were detectable after seizure onset in hypothalamus and globus pallidus but a further reduction in hippocampus (-59%) and significant reductions in substantia nigra (-15%) and caudate putamen (-17%) were detected. Aspartate was elevated in hippocampus, both preictally (+49%) and after seizure onset (+21%) while at the same phases in globus pallidus a consistent reduction (-30%) was observed. The glutamine content increased preictally in globus pallidus (+41%) and hypothalamus (+36%), and in all brain areas during the ictal phase of seizure, the hippocampus exhibiting a dramatic increase (approximately 300%). The contents of serine and alanine were altered in most regions studied only after seizure onset, with the exception of the hippocampus, where a decrease (-41%) of serine was observed preictally.

Alanine↗
PubMed1981

Neonatal body water turnover: a putative index of perinatal morbidity.

The water metabolism of 46 newborn babies was determined during a 10 day period by means of an isotope dilution technique, and correlations were sought with the clinical assessment of the babies by multiple obstetric and pediatric clinical criteria. The babies, 48 to 72 hours of age, were given a single oral dose (2 ml/kg) of deuterated water (D2O), a nonradioactive tracer, and the urinary excretion rate was followed by means of infrared spectrophotometry. After a period of equilibration of the D2O with body water (20 hours), the rate of D2O clearance was found to be a single exponential decay process, thus allowing the fraction of total body water lost each hour (the rate constant) to be calculated for each baby. The median values of the rate constants X 10(4)(h-1) for 14 growth-retarded babies ws 104 (98% confidence limits, 97.8 to 122) compared with 76.3 (67.0 to 80.2) for 16 normal mature babies and 82.1 (73.4 to 90.6) for 16 normal premature babies. These data indicate that, compared with normal mature or normal premature babies, growth-retarded infants have a significantly (P less than 0.05) faster turnover of water during the first 10 days of postnatal life. Since there was little overlap in results between the normally grown and the retarded infants, the measurement of water turnover may provide a useful index of perinatal morbidity.

Body Water↗
PubMed1980

Clomipramine and oral contraceptives: an interaction study--clinical findings.

Forty-six depressed females were admitted to a study primarily designed to investigate the steady-state plasma levels of clomipramine and desmethyl-clomipramine in two groups of patients--one taking oral contraceptives, and one not. Twenty-one patients were taking oral contraceptives and twenty-five were not. Six 'pill'-takers dropped out of the study, two for drug-related reasons, and five non-'pill'-takers, two of whom also developed side-effects. Oral contraceptive takers were found to be significantly more depressed initially than controls, overall. Moreover, when the control group was examined in detail it was found to contain two sub-groups--one moderately depressed and one severely depressed. This latter sub-group was similar to the 'pill'-taking group. Both groups of patients improved similarly. There was no difference in the side-effects experienced. Clinically the study did not suggest that taking oral contraceptives had any influence on the effects of antidepressant medication. It did, however, suggest that either oral contraceptives cause depressed mood and loss of libido or, more likely, that when oral contraceptive takers become depressed these two factors interact to particularly influence mood and libidinous desire.

Adolescent↗