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Biomedical subjects

M Serra

Publications and source records attributed to M Serra.

At least 181 records · Page 10Linked to original sources
PubMed1990

In vivo administration of ethanol enhances the function of the gamma-aminobutyric acid-dependent chloride channel in the rat cerebral cortex.

The effect of in vivo administration of ethanol on the gamma-aminobutyric acidA (GABAA) receptor-coupled chloride channel was studied by measuring ex vivo t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding in the rat cerebral cortex. Intragastric administration of ethanol (0.5-1 g/kg) elicited in 40 min a significant decrease of [35S]TBPS binding to unwashed cortical membrane preparations, an effect mimicked by diazepam (0.5-1 mg/kg, i.p.). However, Scatchard plot analysis indicated that, unlike the case with diazepam, the decrease was entirely due to a reduction in the apparent affinity of [35S]TBPS receptors with no change in the total number of binding sites. Moreover, ethanol, like diazepam, reduced the increase of [35S]TBPS binding elicited by isoniazid (350 mg/kg, s.c.), an inhibitor of the GABAergic transmission. Finally, ethanol markedly potentiated the inhibitory action of diazepam on [35S]TBPS binding. The results suggest that ethanol, like benzodiazepines, enhances the function of the GABAA-coupled chloride channel.

Animals↗
PubMed1990

The general anesthetic propofol enhances the function of gamma-aminobutyric acid-coupled chloride channel in the rat cerebral cortex.

The effect of the general anesthetic propofol on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to unwashed membrane preparations from rat cerebral cortex was studied and compared to that of other general anesthetics (pentobarbital, alphaxalone) which are known to enhance GABAergic transmission. Propofol produced a concentration-dependent complete inhibition of [35S]TBPS binding, an effect similar to that induced by pentobarbital and alphaxalone, although these agents differ markedly in potency (alphaxalone greater than propofol greater than pentobarbital). The concomitant addition of propofol either with alphaxalone or pentobarbital produced an additive inhibition of [35S]TBPS binding, suggesting separate sites of action or different mechanisms of these drugs. Moreover, although bicuculline (0.1 microM) completely antagonized the propofol-induced inhibition of [35S]TBPS binding, the effect of this anesthetic was not due to a direct interaction with the gamma-aminobutyric acidA (GABAA) recognition site. In fact, propofol, like alphaxalone and pentobarbital, markedly enhanced [3H]GABA binding in the rat cerebral cortex. Finally, propofol was able to enhance [3H]GABA binding in membranes previously incubated with the specific chloride channel blocker picrotoxin. Taken together these data strongly suggest that propofol, like other anesthetics and positive modulators of GABAergic transmission, might exert its pharmacological effects by enhancing the function of the GABA-activated chloride channel.

Anesthetics↗
PubMed1990

AIDS victims and heterosexual attitudes.

This study reports on the development of a Likert scale that measures attitudes toward AIDS victims (ATAV) in five phases. A total of 582 undergraduate (means age = 24.2) completed the survey forms, 249 males and 333 females. The results for Phase 1 yielded a scale with high part-whole correlations (.62-.90, p less than .001), corrected split-half reliability (.87, p less than .001), and alpha coefficients (.91, p less than .001). The following phases yielded significant correlations between the ATAV scale and attitudes toward homosexuals (.60, p less than .001), homosexual parenting (.64, p less than .001), other minority groups (.33, .37, p less than .001), capital punishment (-.27 p less than .001), and sexually liberal attitudes (.22, .37, .23, p, less than .025). Attitudes toward homosexuals are the central component in attitudes toward AIDS victims. A varimax rotated factor analysis of the ATAV yielded one primary factor accounting for 85.9% of the variance.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The action of stress and anxiolytic and anxiogenic benzodiazepine receptors ligands on [35S] T-butylbicyclophosphorothionate binding in the rat cerebral cortex.

The effect of foot shock stress on [35S] t-butylbicyclophosphorothionate (TBPS) binding to fresh unwashed membrane preparations from rat cerebral cortex was studied and was compared to those of positive and negative modulators of the GABAergic transmission. 35S-TBPS binding was increased (30%) in cerebral cortex of rats exposed to foot shock compared to the non stressed rats. In contrast, the in vitro addition and the in vivo administration of anxiolytic and positive modulators of the GABAergic transmission inhibited the specific binding of 35S-TBPS. On the other hand, the anxiogenic beta-carbolines DMCM, beta CCM, FG 7142 and beta CCE mimicked in vivo and in vitro the effect of stress. The demonstration that stress, similar to anxiogenic beta-carbolines and opposite to benzodiazepines and anxiolytic beta-carbolines, increases 35S-TBPS binding in the rat cerebral cortex, suggests that some emotional state related to stress and anxiety may result from a diminished GABAergic transmission at the level of the GABA/benzodiazepine receptor/chloride ionophore complex.

Animals↗
PubMed1989

Dramatic increase in nigral t-[35S]butylbicyclophosphorothionate binding sites elicited by the degeneration of the striato-nigral GABAergic pathway: reversal by diazepam.

In rats, the degeneration of the striato-nigral GABAergic pathway caused by the intrastriatal injection of kainic acid induced a marked decrease (65%) of GABA content and glutamic acid decarboxylase (GAD) activity and a dramatic increase (225%) in the binding of t-[35S]butylbicyclophosphorothionate [( 35S]TBPS) to a membrane preparation from the substantia nigra homolateral to the injected striatum. The increase in [35S]TBPS binding in the denervated substantia nigra was exclusively due to an increased density of binding sites (Bmax) with no change in the dissociation constant (kd). The enhancement in [35S]TBPS binding was almost completely reversed by the intraperitoneal administration of diazepam (3 mg/kg) to kainic acid-lesioned rats. Moreover, diazepam produced a significant decrease (30%) in the density of [35S]TBPS binding sites also in the sham-operated side. In contrast the 'in vitro' addition of the GABAA receptor antagonist bicuculline (1 microM) to the membrane preparation from the denervated substantia nigra further increased [35S]TBPS binding. These findings suggest the view that the increase of nigral [35S]TBPS binding is directly related to the inhibition in the function of nigral GABAergic synapses following the loss of the striato-nigral GABAergic pathway. Our results indicate that [35S]TBPS binding to brain structure is a potential tool to reveal alteration in the function of GABAA receptor complex elicited by physiological, pharmacological and pathological conditions.

Animals↗
PubMed1989

Giant cell tumor of bone: a model for the in vitro human osteoclast characterization.

The in vitro growth pattern of cells obtained from bioptic material of ten patients with giant cell tumor of bone (GCT) was investigated. Cytochemical reactions and monoclonal antibodies raised against macrophage markers were tested on the two histologically identifiable GCT cell populations. Only monoclonal antibody EBM/11 stained both mononuclear and giant cells. EBM/11 positivity and resistance of acid phosphatase to high doses of tartrate strongly suggest that both mononuclear and giant cells belong to the same lineage.

Acid Phosphatase↗
PubMed1989

On the asymmetry of the primary branching of vagal sensory axons: possible role of the supporting tissue.

Central and peripheral nonmedullated processes of vagal nodosal neurons of the cat were studied in normal nerves and after regeneration along their anatomical course and along the hypoglossal nerve. Nonmedullated fibers above the ganglion and in the root had comparable sizes (approximately 0.37 micron2) and caliber distribution. Below the ganglion, the cross-sectional area increased to 1.0 micron2. In axons of equal caliber, supranodosal and radicular fibers had similar microtubular densities while infranodosal fibers had two- to threefold that of the former. Regenerated fibers were studied after a recovery period of 6-9 months. Regrown axons were smaller than their parent axons; in turn, these were smaller than normal axons. This holds for central and peripheral nodosal branches, for homologous and heterologous regeneration. Regrown peripheral branches, either along their anatomical pathway or along the hypoglossal nerve, showed no change in microtubular density. Central branches exhibited their characteristic microtubular content when they regenerated along their anatomical course, but when regrowth took place along the hypoglossal nerve, the original low microtubular content of these branches increased to match the high content of peripheral fibers; parent central axons also shifted their microtubular content toward the pattern of peripheral fibers. We propose that the supporting tissue participates in specifying the organization of axonal microtubules.

Animals↗
PubMed1989

Isoniazid, an inhibitor of GABAergic transmission, enhances [35S]TBPS binding in rat cerebral cortex.

Isoniazid, administered to rats one hour before killing produced a dose-dependent enhancement of [35S]t-butylbiciclophosphorothionate ([35S]TBPS, 2 nM) measured ex vivo in unwashed membrane preparation of the cerebral cortex. Saturation experiments revealed that the effect of isoniazid was due to an increase (+36%) in the total number of [35S]TBPS binding sites. Diazepam (3 mg/kg i.p.) administered 15 min after isoniazid antagonized the enhancement of [35S]TBPS binding elicited by isoniazid. Moreover, diazepam itself induced a significant decrease (-30%) in the total number of [35S]TBPS binding sites. These results provide the first direct evidence that 'in vivo' alterations in the function of the GABA-dependent chloride channel can be detected in vitro by studying the binding of [35S]TBPS to its recognition sites in the GABAA receptor complex. Our finding suggests a new model suitable to study biochemically the function of GABAergic synapses under various physiological and pharmacological conditions.

Animals↗
PubMed1989

Enhancement of GABAergic transmission by zolpidem, an imidazopyridine with preferential affinity for type I benzodiazepine receptors.

The effect of zolpidem, an imidazopyridine derivative with high affinity at the type I benzodiazepine recognition site, on the function of the GABAA/ionophore receptor complex was studied in vitro. Zolpidem, mimicking the action of diazepam, increased [3H]GABA binding, enhanced muscimol-stimulated 36Cl- uptake and reduced [35S]TBPS binding in rat cortical membrane preparations. Zolpidem was less effective than diazepam on the above parameters. Zolpidem induced a lower increase of [3H]GABA binding (23 vs. 35%) and muscimol-stimulated 36Cl- uptake (22 vs. 40%) and a smaller decrease of [35S]TBPS binding (47 vs. 77%) than diazepam. The finding that zolpidem enhanced the function of GABAergic synapses with an efficacy qualitatively and quantitatively different from that of diazepam suggests that this compound is a partial agonist at the benzodiazepine recognition site. Thus, our results are consistent with the view that the biochemical and pharmacological profile of a benzodiazepine recognition site ligand reflects its efficacy to enhance GABAergic transmission. Whether the preferential affinity of zolpidem at the type I site is involved in its atypical biochemical and pharmacological profile remains to be clarified.

Animals↗
PubMed1988

Cholecystokinic activity of N alpha-hydroxysulfonyl-[Nle28,31]CCK26-33 analogues modified at the C-terminal residue.

Three new analogues of N alpha-hydroxysulfonyl-[Nle28,31]CCK26-33 are reported in which the C-terminal L-Phe33 residue has been replaced by L-Leu, D-Phe or N-methyl-L-Phe. Biological evaluation in a series of binding and bioassays demonstrates that both L-stereochemistry and an aromatic side chain at position-33 are essential for full agonist activity. While the L-Leu33 and D-Phe33 analogues had reduced potencies in stimulating contraction of the guinea pig ileum or gall bladder, the D-Phe33 analogue was fourfold selective for the ileum. This latter analogue also exhibited apparent partial agonism in the rat pancreatic amylase release assay. The N-methyl-L-Phe33 analogue was almost equipotent to the parent analogue in all bioassays, suggesting that this modification might be useful for introducing enzymatic stability in CCK analogues.

Acetylcholine↗
PubMed1988

Foot-shock stress and anxiogenic beta-carbolines increase t-[35S]butylbicyclophosphorothionate binding in the rat cerebral cortex, an effect opposite to anxiolytics and gamma-aminobutyric acid mimetics.

The effect of foot-shock stress on t-[35S]butylbicyclophosphorothionate [( 35S]TBPS) binding to fresh unwashed membrane preparations from rat cerebral cortex was studied and was compared to those of GABAA receptor agonists and antagonists and to positive and negative modulators of the GABAergic transmission. [35S]TBPS binding was increased in the cerebral cortex of rats exposed to foot shock compared to that of nonstressed rats. Scatchard analysis revealed that the effect of foot shock was due to an increase in the total number of [35S]TBPS binding sites. In contrast, the in vitro addition of muscimol or GABA induced a dose-dependent inhibition of [35S]TBPS binding, an effect abolished by the concomitant addition of the GABA receptor antagonist, bicuculline, which, per se, enhanced [35S]TBPS binding by 73%. Thus, bicuculline, similar to stress, increased [35S]TBPS binding in the same membrane preparation. In contrast to stress, the anxiolytic and positive modulators of the GABAergic transmission (ZK 93423, ZK 91296, and diazepam) inhibited the specific binding of [35S]TBPS in a concentration-dependent manner. The greatest inhibitory effect was produced by ZK 93423 at 30 microM (31% of control), followed by diazepam (54% of control) and by the partial agonist ZK 91296 (61% of control). Scatchard plot analysis indicated that the inhibition induced by ZK 93423 and diazepam was due to a decrease in the density of [35S]TBPS recognition sites. On the other hand, the anxiogenic beta-carbolines DMCM and FG 7142 mimicked the effect of stress. Thus, at a 10 microM concentration, DMCM and FG 7142 increased [35S]TBPS binding by 22% and 26%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The intact human neuroblastoma cell (SH-SY5Y) exhibits high-affinity [3H]pirenzepine binding associated with hydrolysis of phosphatidylinositols.

The binding of [3H]pirenzepine to a human neuroblastoma cell line (SH-SY5Y) and its correlation with hydrolysis of phosphatidylinositols were characterized. Specific [3H]pirenzepine binding to intact cells was rapid, reversible, saturable, and of high affinity. Kinetic studies yielded association (k+1) and dissociation (k-1) rate constants of 5.2 +/- 1.4 X 10(6) M-1 min-1 and 1.1 +/- 0.06 X 10(-1) min-1, respectively. Saturation experiments revealed a single class of binding sites (nH = 1.1) for the radioligand with a total binding capacity of 160 +/- 33 fmol/mg protein and an apparent dissociation constant of 13 nM. The specific [3H]pirenzepine binding was inhibited by the presence of selected muscarinic drugs. The order of antagonist potency was atropine sulfate greater than pirenzepine greater than AF-DX 116, with K0.5 of 0.53 nM, 2.2 nM, and 190 nM, respectively. The binding properties of [3H](-)-quinuclidinyl benzilate and its quaternary derivative [3H](-)-methylquinuclidinyl benzilate were also investigated. The muscarinic agonist carbachol stimulated formation of inositol phosphates which could be inhibited by muscarinic antagonists. The inhibition constants of pirenzepine and AF-DX 116 were 11 nM and 190 nM, respectively. In conclusion, we show that the nonclassical muscarinic receptor antagonist [3H]pirenzepine identifies a high-affinity population of muscarinic sites which is associated with hydrolysis of phosphatidylinositols in this human neuroblastoma cell line.

Atropine↗