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Biomedical subjects

C D Richards

Publications and source records attributed to C D Richards.

At least 91 records · Page 5Linked to original sources
PubMed1985

Stereospecific binding sites for [3H]nicotinamide adenine dinucleotide in the rat brain.

NAD is a potent inhibitor of electrical activity in the dentate gyrus of the guinea pig hippocampus. NAD is rapidly degraded by an NADase enzyme present on synaptosomal membranes that we have recently found to be inhibited by nicotinamide mononucleotide. In this report we have characterised the binding sites present on brain membranes for [3H]NAD in the presence of this inhibitor. We have demonstrated two binding sites of KdS 49 nM and 4.26 microM that are modulated by GTP. From structure-activity studies we have shown the binding to be stereospecific for the beta-isomer of NAD requiring the whole of the molecule for full receptor affinity. The binding sites are distinct from those reported for adenosine and their presence has significance for the physiological role of NAD in the mammalian brain.

Animals↗
PubMed1985

Multinucleate giant cells in murine and rat lungs during Nippostrongylus brasiliensis infections. A study of the kinetics of the response in vivo, cytochemistry, IgG- and C3-mediated functions.

The cytochemical and functional characteristics of broncho-alveolar multinucleate giant cells and the kinetics of the giant cell response in the lungs of mice and rats during Nippostrongylus brasiliensis infection were studied. Primary infections resulted in significantly increased numbers of recoverable giant cells for up to 30 and 50 days in rats and mice, respectively. During secondary infections in the rat the giant cell response was more rapid and greater in magnitude than in a primary infection, suggesting that it was immunologically mediated. The giant cells displayed decreased C3- and IgG-dependent binding or phagocytic potential compared with mononucleate alveolar macrophages. Fusion of mononucleate alveolar macrophages into giant cells may therefore compromise complement and antibody dependent helminthocidal activity of these cells.

Animals↗
PubMed1985

IgA-mediated phagocytosis by mouse alveolar macrophages.

Ingestion of antibody-opsonized sheep red blood cells by murine alveolar and peritoneal exudate macrophages was studied. Alveolar macrophages or peritoneal macrophages were isolated by lavage and incubated with TNP-SRBC, which had been preincubated with anti-DNP IgG, IgA, and IgE. Significant enhancement of phagocytosis by alveolar macrophages of TNP-SRBC was mediated by all classes of antibody examined, most markedly with IgG and less so with IgA and IgE. Enhancement of phagocytosis by peritoneal macrophages was mediated by IgG and IgE, but not by IgA. These results suggest that the interaction of IgA and Fc receptors for IgA on alveolar macrophages may increase the level of this cell's function in the mammalian lung to clear pathogens and immune complexes from the alveolar spaces.

Animals↗
PubMed1984

Changes in free-calcium levels and pH in synaptosomes during transmitter release.

The free cytoplasmic Ca2+ concentration [( Ca2+]i) in rat brain synaptosomes estimated by the indicator quin 2 is 104 +/- 8 nM (S.D.) in artificial cerebrospinal fluid (1.2 mM Ca2+), but decreases at lower Ca2+ concentrations in the medium. The presence of quin 2 in the synaptosomes does not affect either the spontaneous release of transmitter (gamma-aminobutyric acid) or the release induced by K+ depolarisation. In quin 2-loaded synaptosomes, depolarisation by K+ causes an abrupt increase in [Ca]i (less than 2-fold) that is approximately proportional to the extent of depolarisation, whereas depolarisation by veratrine alkaloids produces a slow rise in [Ca]i. The increase in [Ca]i produced by K+ depolarisation does not occur in the absence of Ca2+ in the medium. The data are consistent with a direct correlation between [Cai] and transmitter release in functional synaptosomes. The pH in synaptosomes estimated by the indicator quene 1 is 7.04 +/- 0.07 and is stable in media containing 5 mM bicarbonate. The pH in synaptosomes was decreased by protoveratrine but not by K+ depolarisation.

Aminoquinolines↗
PubMed1984

Degradation of NAD by synaptosomes and its inhibition by nicotinamide mononucleotide: implications for the role of NAD as a synaptic modulator.

We have found NAD to be rapidly degraded by extracellular enzymes present on intact rat brain synaptosomes. The enzyme involved had the specificity of an NADase cleaving the molecule at the nicotinamide-glycoside linkage and was inhibited by nicotinamide mononucleotide (NMN). This inhibitor did not displace specific binding of NAD to rat brain membranes or affect electrical activity in the guinea pig hippocampus. Therefore, inclusion of NMN in binding assays allowed unambiguous demonstration of two specific NAD binding sites on rat brain synaptosomal membranes (KD1, 82 nM, KD2, 1.98 microM). The depressant action of NAD on the evoked synaptic activity of the guinea pig hippocampus was not blocked after inhibition of NAD degradation with NMN. The physiological implications of these results for the function of NAD as a neurotransmitter or neuromodulator in the CNS are discussed.

Adenosine↗
PubMed1984

Effect of lesions of the olfactory bulb on the levels of amino acids and related enzymes in the olfactory cortex of the guinea pig.

Olfactory bulb removal and consequential degeneration of the lateral olfactory tract led to a decrease in the levels of glutaminase and malate dehydrogenase in the ipsilateral olfactory cortex. These changes in enzyme activity may account for the well established decrease in the levels of aspartate and glutamate in the olfactory cortex following ipsilateral bulbectomy. The level of glutamine synthetase, a glial marker enzyme, was slightly increased while the activities of glutamate decarboxylase, glutamate dehydrogenase, and glutamate oxaloacetic transaminase were unchanged.

Amino Acids↗
PubMed1984

Temperature-dependence of the action of nerve blocking agents and its relationship to membrane-buffer partition coefficients: thermodynamic implications for the site of action of local anaesthetics.

The local anaesthetic action of a series of nerve blocking agents was examined at temperatures between 4 degrees C and 20 degrees C in isolated sciatic nerves from cold-adapted frogs. Cooling alone had little effect on the amplitude of the action potential but the conduction velocity was decreased and the duration increased. Cooling had little effect on the local anaesthetic action of the short chain alkanols but that of the long chain alkanols, benzyl alcohol, benzocaine and pentobarbitone was markedly enhanced. The partition of both short and long chain alkanols and of pentobarbitone into a liposome suspension of similar composition to axonal membrane lipids was reduced by cooling from 40 degrees C to 4 degrees C. The results are not compatible with the lipid hypotheses of anaesthetic action. The implications for the nature of the site of action are discussed.

Action Potentials↗
PubMed1983

Actions of general anaesthetics on synaptic transmission in the CNS.

This article reviews the actions of general anaesthetics on synapses in the mammalian central nervous system. It is shown that during general anaesthesia, anaesthetics act primarily on the chemical transmission process itself and do not affect the conduction of impulses in nerve axons or change the electrical excitability of neurones. Virtually all general anaesthetics depress excitatory synaptic transmission at concentrations required for surgical anaesthesia but some, notably the barbiturates, also increase the intensity of inhibitory synaptic transmission. Detailed analysis has found that small concentrations of barbiturates increase the amount of inhibitory transmitter released but decrease the amount of excitatory transmitter released. In addition to these effects on the neurosecretory process, anaesthetics directly affect the sensitivity of the postsynaptic receptors to transmitter substances, although the effects vary between anaesthetics and receptors. It is concluded that general anaesthesia results from a summation of a number of effects which together tend to depress the excitability of the CNS as a whole.

Anesthesia, General↗
PubMed1983

Nicotinamide adenine dinucleotide depresses synaptic transmission in the hippocampus and has specific binding sites on the synaptic membranes.

The electrical activity of transverse slices of hippocampus was used as a bioassay in which extracts of fresh brain tissue were screened for biological activity. A factor that depressed synaptic transmission was identified as nicotinamide adenine dinucleotide (NAD). This depressant action of NAD could be observed at concentrations in the range 1-10 microM and the degree of depression was monotonically related to the concentration of NAD in the bathing medium. NAD did not affect the antidromic invasion of the granule cells nor did it alter the relationship between the electrically evoked excitatory postsynaptic field potential (e.p.s.p.) and the population discharge of the granule cells (population spike). These results suggest that NAD did not affect the electrical excitability of the neuronal membranes. NAD had little effect on the sensitivity of granule cells to iontophoretically applied L-glutamate, the putative excitatory transmitter for the perforant path-granule cell pathway. Pure synaptosomal membranes, free of mitochondria, had two binding sites for NAD: a high affinity site with a Kd of 1 microM and a low affinity site with a Kd of 17 microM. These sites were similar in affinity to those of mitochondria, although the density of the high affinity sites was 5 X greater in the synaptosomal membranes. Adenosine had a relatively weak affinity for the NAD binding sites. It was concluded that NAD probably depressed synaptic transmission in the dentate gyrus by binding to sites on the presynaptic nerve terminal and reducing the amount of transmitter released by a nerve impulse. The physiological significance of this view is discussed.

Animals↗
PubMed1982

Electrophysiological evidence for a somatotopic sensory projection to the striatum of the rat.

The somatosensory projection to the striatum of the rat was investigated by electrophysiological mapping. Fifty-five units were encountered that responded to specific forms of stimulation delivered to particular parts of the body. Units that responded to stimuli delivered to the hindlimb, scrotum and tail were found in the most caudal regions of the striatum while those that responded to stimulation of the forelimb, head and neck were found in the anterior regions of the striatum. The results strongly suggest that there is, in the striatum of the rat, a sensory map of the body that is organized on topographical principles.

Animals↗
PubMed1982

The actions of pentobarbitone, procaine and tetrodotoxin on synaptic transmission in the olfactory cortex of the guinea-pig.

1 It has been suggested that the depression of excitatory synaptic potentials produced by general anaesthetics can be attributed to a partial blockade of impulse conduction in the terminal branches of axons. This hypothesis has been tested by comparing the actions of pentobarbitone, procaine and tetrodotoxin (TTX) on synaptic transmission in the guinea-pig olfactory cortex. 2 Pentobarbitone (0.1-0.3mM) depressed the evoked synaptic potentials without any significant depression of impulse conduction in the afferent fibres of the lateral olfactory tract (1.o.t). It had no effect on the electrical excitability of either the l.o.t axons or the postsynaptic neurones. 3 Tetrodotoxin (TTX; 1-5x10(-8 M) slowed conduction of impulses in the l.o.t. and decreased the amplitude of the l.o.t compound action potential in proportion to the concentration applied. All concentrations of TTX elevated the electrical threshold of the l.o.t. axons and there was evidence to suggest that the threshold of the postsynaptic neurones was also elevated. The synaptic potentials were depressed in direct proportion to the depression of the l.o.t. compound action potential. 4 Procaine (0.1-0.5 mM) exhibited a pattern of activity intermediate between pentobarbitone and TTX. The most marked effect, seen at all concentrations tested, was a slowing of impulse conduction and a decrease in the electrical excitability of the l.o.t. axons. 5 It is concluded that general anaesthetics (exemplified by pentobarbitone) depress synaptic transmission by interfering with the processes involved in chemical transmission and not by blocking impulse conduction in the terminal branches of afferent nerves.

Animals↗
PubMed1981

Additive and non-additive effects of mixtures of short-acting intravenous anaesthetic agents and their significance for theories of anaesthesia.

1 The potency of a series of short-acting anaesthetics was established by measuring the duration of the loss of righting reflex following a single bolus injection into the tail vein of male Wistar rats. The agents were, in order of potency, etomidate, alphaxalone, methohexitone, alphadalone acetate and propanidid.2 The potency of binary mixtures of these agents was also assessed to see whether the anaesthetic effects of different agents were additive as classical theories of anaesthesia suggest. Mixtures of alphaxalone and alphadalone acetate, alphaxalone and propanidid and methohexitone and propanidid all showed simple additive effects. Mixtures of alphaxalone and etomidate and of alphaxalone and methohexitone showed a greater potency than would be expected if their effects were simply additive. Mixtures of etomidate and methohexitone were not examined.3 Mixtures of alphaxalone and either methohexitone or pentobarbitone produced a greater depression of synaptic transmission in in vitro preparations of guinea-pig olfactory cortex than would have been expected from the sum of the activities of the individual anaesthetics. Other combinations of anaesthetics did not show similar effects although the interaction between alphaxalone and etomidate was not examined.4 Neither alphaxalone nor pentobarbitone affected the membrane: buffer partition coefficient of the other for a model membrane system.5 These results are interpreted as evidence against the classical unitary hypotheses of anaesthetic action based on correlations of anaesthetic potency with lipid solubility and as supporting the view that different anaesthetics act on different structures in the neuronal membranes to produce anaesthesia.

Anesthesia, Intravenous↗