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Biomedical subjects

A Galvan

Publications and source records attributed to A Galvan.

10 recordsLinked to original sources

Naloxone blocks the antianxiety but not the motor effects of benzodiazepines and pentobarbital: experimental studies and literature review.

The role of opioid systems in the anticonflict effect of chlordiazepoxide, diazepam and pentobarbital was evaluated with a modified Vogel procedure. First, morphine, ineffective by itself, was combined with subeffective or marginally effective doses of the benzodiazepines in order to detect possible potentiation. However, the combined treatment reduced licking in the Vogel procedure as well as in a licking test where no shock was administered. Several doses of the benzodiazepines and pentobarbital were then administered in combination with several doses of the opiate antagonist naloxone. A dose-dependent inhibition of anticonflict effect was obtained. In an additional experiment, it was shown that naloxone blocked the effects of diazepam in the elevated plus-maze procedure. Motor deficiencies, as evaluated with a rotarod test, produced by the benzodiazepines and pentobarbital could not be antagonized by naloxone. It is concluded that opioids are important for the anticonflict but not for the motor effects of these drugs. An analysis of published studies concerning the interaction of opioids and benzodiazepines in several procedures supposed to reflect anxiolytic effects shows that the inhibition obtained with naloxone is reliable and not procedure specific. The mechanisms by which opiate antagonists produce this inhibition of anticonflict activity are not known. It is tentatively suggested that opioid activation associated with stress may be a necessary component of anxiolysis.

Animals

Reward and reinforcement produced by drinking sucrose: two processes that may depend on different neurotransmitters.

The capacity of sucrose drinking to produce conditioned place preference (CPP) and the effects of dopamine and opioid receptor blockade on acquisition of this preference and on sucrose consumption were evaluated. The establishment of place preference would reflect the reinforcing consequences of drinking, while the amount of sucrose solution consumed would illustrate its rewarding properties. Male Wistar rats were allowed to drink an 18% sucrose solution. No deprivation was used. Drinking produced place preference, and this was blocked with cis(z)-flupentixol, 0.5 mg/kg. Naloxone, 16 mg/kg, not only blocked place preference, but also reduced sucrose consumption. In fact, animals consumed amounts similar to those consumed by rats given plain water. Lower doses of naloxone, 1 and 4 mg/kg, also decreased sucrose consumption, but 1 mg/kg did not block place preference. As the dopamine antagonist did not affect consumption at a dose that inhibited conditioned place preference, it is suggested that dopamine is critical for the establishment of reinforcement produced by sucrose. Opioids seem to be more important for the rewarding effect because naloxone reduces drinking even at a dose that does not affect place preference.

Animals

Structural organization of the lens fiber cell plasma membrane protein MP18.

The 18,000-dalton bovine lens fiber cell intrinsic membrane protein MP18 was phosphorylated on a serine residue by both cAMP-dependent protein kinase and protein kinase C. In addition, this protein bound calmodulin and was recognized by a monoclonal antibody (2D10). These different regions were localized using enzymatic and chemical fragmentation of electrophoretically purified MP18 that had been phosphorylated with either cAMP-dependent protein kinase or protein kinase C. Partial digestion of 32P-labeled MP18 with protease V8 resulted in a Mr = 17,000 peptide that bound calmodulin, but neither contained 32P or was recognized by the monoclonal antibody 2D10. Furthermore, the 17-kDa peptide had the same N-terminal amino acid sequence as MP18. Thus, the monoclonal antibody 2D10 recognition site and the protein kinase phosphorylation site(s) are close together and confined to a small region in the C terminus of MP18. This conclusion was confirmed in experiments where MP18 was fragmented with trypsin, endoproteinase Lys-C, or CNBr. The location of the phosphorylation site was confirmed by sequencing the small 32P-labeled, C-terminal peptide that resulted from protease V8 digestion of 32P-labeled MP18. This peptide contained a consensus sequence for cAMP-dependent protein kinase.

Amino Acid Sequence

Calcium regulation by lens plasma membrane vesicles.

The role of the plasma membrane in the regulation of lens fiber cell cytosolic Ca2+ concentration has been examined using a vesicular preparation derived from calf lenses. Calcium accumulation by these vesicles was ATP dependent, and was releasable by the ionophore A23187, indicating that calcium was transported into a vesicular space. Calcium accumulation was stimulated by Ca2+ (K1/2 = 0.08 microM Ca2+) potassium (maximally at 50 mM K+), and cAMP-dependent protein kinase; it was inhibited by both vanadate (IC50 = 5 microM) and the calmodulin inhibitor R24571 (IC50 = 5 microM), indicating that this pump was plasma-membrane derived and likely calmodulin dependent. Valinomycin, in the presence of K+, stimulated calcium uptake, suggesting that the calcium pump either countertransports K+, or is regulated in an electrogenic fashion. Inhibition of calcium uptake by selenite and p-chloromercuribenzoate demonstrates the presence of an essential -SH group(s) in this enzyme. Calcium release from calcium-filled lens vesicles was enhanced by Na+, demonstrating that these vesicles also contain a Na:Ca exchange carrier. p-Chloromercuribenzoate and p-chloromercuribenzoate sulfonic acid also promoted calcium release from calcium-filled vesicles, suggesting that this release, like calcium uptake, is in part mediated by a cysteine-containing protein. We conclude that lens fiber cell cytosolic Ca2+ concentration could be regulated by a number of plasma membrane processes. The sensitivity of both calcium uptake and release to -SH reagents has implications in lens cataract formation, where oxidation of lens proteins has been proposed to account for the elevated cytosolic Ca2+ in this condition.

4-Chloromercuribenzenesulfonate

Ionic and substrate requirements of the high affinity calcium pumping ATPase in endoplasmic reticulum of pancreas.

1. Calcium transport and ATPase activities were determined in microsomal vesicles from pancreatic tissue enriched in endoplasmic reticulum membranes. 2. Calcium transport and ATPase share the following properties: (i) magnesium was required with a K0.5 of 0.7 mM and maximal pumping ATPase activity at 5 mM Mg-ATP; (ii) at saturating magnesium concentrations, calcium increased ATP splitting activity up to three times with an apparent K0.5 close to 0.3 microM calcium; (iii) potassium stimulated the high calcium affinity Mg2+-dependent ATPase and calcium transport. 3. The properties of the calcium pumping system fulfil the cationic and substrate requirements from a physiological point of view.

Animals

Gastric bezoars. A technique of endoscopic removal.

Gastric bezoar formation is an uncommon sequela of gastroduodenal surgery or unusual eating habits. Because they generally produce severe symptoms, their removal is always necessary. Previously, this required surgical extirpation or slow enzymatic dissolution. We present here an endoscopic procedure for bezoar removal utilized successfully in five patients with vegetable-mucus bezoars. This technique employs a jet spray of water under direct vision to mechanically disrupt the bezoar, which may then be removed using a large gastric lavage tube. This procedure is simple, safe, and rapid and is therefore recommended as an alternative to surgical removal or enzymatic dissolution of gastric bezoars.

Bezoars