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S Couture

Publications and source records attributed to S Couture.

7 recordsLinked to original sources
PubMed2001

Some of the effects of the selective sigma ligand (+)pentazocine are mediated via a naloxone-sensitive receptor.

Recently, in an attempt to isolate the nonopioid sigma receptor, Su and colleagues purified a protein from rat liver and brain which appeared to resemble the original sigma opioid receptor as proposed by Martin in 1976, and for which the nonopiate sigma-1 ligand (+)pentazocine presents a high affinity. Previous in vivo electrophysiological studies from our laboratory have demonstrated that several selective sigma-1 ligands potentiate the neuronal response to NMDA. The goal of the present series of experiments was to assess the effects of some selective sigma-1 ligands on the potentiation of the NMDA response and to determine if this potentiation was mediated by the naloxone-sensitive sigma receptor. Extracellular unitary recordings from pyramidal neurons of the CA3 region of the rat dorsal hippocampus were obtained. The sigma-1 ligands BD 737, L 687-384, and JO-1784 (igmesine), administered intravenously at low doses, potentiated the NMDA response but the opiate antagonist naloxone failed to reverse this potentiation. However, the potentiation of the NMDA response induced by the sigma-1 ligand (+)pentazocine was suppressed by naloxone but not by the mu antagonist cyprodime hydrobomide, the kappa antagonist DIPPA nor by the delta antagonist naltrindole. (+/-) Cyclazocine, which presents a high affinity for the above-mentioned sigma-opiate receptor acted as an antagonist by suppressing the potentiation of the NMDA response induced by both JO-1784 and (+)pentazocine. These results suggest that the effects induced by some sigma-1 ligands may, in fact, be sensitive to naloxone while others may not. The original classification of sigma receptors as opiates might have been partly accurate.

Action Potentials↗
PubMed1998

Modulation of the neuronal response to N-methyl-D-aspartate by selective sigma2 ligands.

It has now been accepted for several years that sigma (sigma) receptors exist in, at least, two distinct entities denoted sigma1 and sigma2. Previous electrophysiological studies from our laboratory have demonstrated that several selective sigma1 ligands potentiate the neuronal response to NMDA. The nonselective sigma1/sigma2 ligand DTG also potentiates the NMDA response. However, when DTG is administered at doses between 3 and 40 microg/kg, the increase of NMDA-induced activation turns to an epileptoid activity. Until recently, the physiological role of sigma2 receptors had been less studied due to the lack of selective sigma2 ligands. The goal of the present electrophysiological studies was to assess the effect of the intravenous administration of new selective sigma2 ligands on the neuronal response to NMDA in the CA3 region of the rat dorsal hippocampus. Lu 28-179 and BD 1008 potentiated dose-dependently the NMDA response and generated bell-shaped dose-response curves. These ligands failed to generate any epileptoid activity on their own but the subsequent administration of a low dose of a sigma1 agonist (JO-1784) induced an epileptoid activity. Interestingly, the potentiations of the NMDA response induced by Lu 28-179 or BD 1008 were not reversed by haloperidol, by the neurosteroid progesterone, nor by the selective sigma1 antagonist NE-100. Ibogaine, a high affinity sigma2 ligand, slightly increases the NMDA response, which was reversed by progesterone. These data suggest that, similarly to sigma1 ligands, sigma2 agonists potentiate the NMDA response and that the coactivation of sigma1 and sigma2 receptors could be necessary to induce an epileptoid activity. They also suggest that haloperidol may not act as a sigma2 antagonist and that several subtypes of sigma2 receptors could exist.

Animals↗
PubMed1991

A multisubunit ribozyme that is a catalyst of and template for complementary strand RNA synthesis.

Derivatives of the sunY self-splicing intron efficiently catalyzed the synthesis of complementary strand RNA by template-directed assembly of oligonucleotides. These ribozymes were separated into three short RNA fragments that formed active catalytic complexes. One of the multisubunit sunY derivatives catalyzed the synthesis of a strand of RNA complementary to one of its own subunits. These results suggest that prebiotically synthesized oligonucleotides might have been able to assemble into a complex capable of self-replication.

Animals↗
PubMed1990

Phylogenetic and genetic evidence for base-triples in the catalytic domain of group I introns.

Understanding the mechanisms by which ribozymes catalyse chemical reactions requires a detailed knowledge of their structure. The secondary structure of the group I introns has been confirmed by comparison of over 70 published sequences, by chemical protection studies, and by genetic experiments involving compensatory mutations. Phylogenetic data can also be used to identify tertiary interactions in RNA molecules. This was first done by Levitt, who predicted tertiary interactions in transfer RNA, which were subsequently confirmed by X-ray crystallography. More recently, sequence comparison data have been used to predict tertiary interactions in ribosomal RNA. We have searched a complete alignment of the core regions of group I introns for evolutionary covariations that could not be ascribed to classical Watson-Crick or wobble base pairings. Here we describe two examples of phylogenetic covariation that are most simply explained by postulating hydrogen-bonded base-triples similar to those found in tRNA. Genetic experiments with the Tetrahymena and sunY introns confirm the importance of these interactions for the structure of the ribozyme.

Animals↗
PubMed1990

Mutational analysis of conserved nucleotides in a self-splicing group I intron.

We have constructed all single base substitutions in almost all of the highly conserved residues of the Tetrahymena self-splicing intron. Mutation of highly conserved residues almost invariably leads to loss of enzymatic activity. In many cases, activity could be regained by making additional mutations that restored predicted base-pairings; these second site suppressors in general confirm the secondary structure derived from phylogenetic data. At several positions, our suppression data can be most readily explained by assuming non-Watson-Crick base-pairings. In addition to the requirements imposed by the secondary structure, the sequence of the intron is constrained by "negative interactions", the exclusion of particular nucleotide sequences that would form undesirable secondary structures. A comparison of genetic and phylogenetic data suggests sites that may be involved in tertiary structural interactions.

Animals↗
PubMed1990

Preservation of short-term energy balance in clinically stable patients with AIDS.

Malnutrition in patients with acquired immune deficiency syndrome (AIDS) is common and multifactorial. The possible causes of malnutrition were evaluated by performing studies of energy balance in five clinically stable outpatients with AIDS, six seronegative homosexual control subjects, and five seronegative heterosexual control subjects. The AIDS group was significantly depleted of body cell mass compared with the control subjects but the values did not change significantly over 6 wk. Food intake was normal in the AIDS group whereas intestinal absorptions of the pentose sugar xylose and of the triglyceride triolein were both significantly diminished. The AIDS patients were hypometabolic as compared with the control subjects and with predictions of metabolic rate based on the Harris-Benedict equation. We conclude that short-term energy balance can be maintained in clinically stable patients with AIDS. Hypometabolism is an appropriate metabolic response to the combination of body-cell-mass depletion and nutrient malabsorption.

Acquired Immunodeficiency Syndrome↗