RESUMEN
We investigated the effects of the noble gas argon on the expression of locomotor sensitization to amphetamine and amphetamine-induced changes in dopamine release and mu-opioid neurotransmission in the nucleus accumbens. We found (1) argon blocked the increase in carrier-mediated dopamine release induced by amphetamine in brain slices, but, in contrast, potentiated the decrease in KCl-evoked dopamine release induced by amphetamine, thereby suggesting that argon inhibited the vesicular monoamine transporter-2; (2) argon blocked the expression of locomotor and mu-opioid neurotransmission sensitization induced by repeated amphetamine administration in a short-term model of sensitization in rats; (3) argon decreased the maximal number of binding sites and increased the dissociation constant of mu-receptors in membrane preparations, thereby indicating that argon is a mu-receptor antagonist; (4) argon blocked the expression of locomotor sensitization and context-dependent locomotor activity induced by repeated administration of amphetamine in a long-term model of sensitization. Taken together, these data indicate that argon could be of potential interest for treating drug addiction and dependence.
Asunto(s)
Anfetamina/farmacología , Argón/farmacología , Locomoción/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Receptores Opioides mu/antagonistas & inhibidores , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Anfetamina/antagonistas & inhibidores , Animales , Sensibilización del Sistema Nervioso Central/efectos de los fármacos , Sensibilización del Sistema Nervioso Central/fisiología , Dopamina/fisiología , Masculino , Núcleo Accumbens/fisiología , Ratas , Ratas Sprague-Dawley , Proteínas de Transporte Vesicular de Monoaminas/fisiologíaRESUMEN
This study aimed at demonstrating that the neoprene wetsuit provides not only thermal protection. Compression it exerts on the diver's shell significantly impacts hydromineral homeostasis by restraining the systemic vascular capacity and secondarily increasing urine output on dry land and during scuba diving. 8 healthy divers underwent five 2-h sessions: sitting out of water in trunks (control situation), sitting out of water wearing a wetsuit, and 3 wetsuit scuba-immersed sessions at 1, 6 and 12 msw depth, respectively. Urine volumes and blood samples were collected. Hemoglobin (Hb), hematocrit (Ht) and plasma sodium concentration were measured. Interface pressure between the garment and the skin was measured at 17 sites of the body shell, with a pressure transducer. Mean interface pressures between wetsuit and skin amounted to: 25.8±2.8 mm Hg. Whatever the depth, elastic recoil tension of wetsuit material was unchanged by immersion. Weight loss was respectively 2 and 3 times greater when wetsuit was worn out of water (430 g) and during immersion (710 g) than when divers did not wear any wetsuit out of water (235 g; p<0.05). Urine volume accounted for 85% of weight loss in either session. Weight loss and urine volume were similar whatever immersion depth. The decrease in plasma volume amounted to 8% of urine volume when divers did not wear any wetsuit out of water, and to 30% when wetsuit was worn out of water or during immersion. Diving wetsuit develops a pressure effect that alters diver's hydromineral homeostasis. During immersion, the wetsuit pressure merges into the larger main effect of hydrostatic pressure to reduce water content of body fluids, unrelated to immersion depth.
Asunto(s)
Buceo/fisiología , Neopreno , Volumen Plasmático/fisiología , Ropa de Protección , Adulto , Líquidos Corporales/fisiología , Hematócrito , Hemoglobinas/metabolismo , Homeostasis , Humanos , Masculino , Presión , Sodio/sangre , Orina/fisiología , Pérdida de Peso/fisiologíaRESUMEN
Nitrogen narcosis occurs in humans at around 0.4 MPa (4 ATA). Hydrogen narcosis occurs between 2.6 and 3.0 MPa. In rats, nitrogen disturbances occur from 1 MPa and a loss of righting reflex around 4 MPa. Neurochemical studies in striatum of rats with nitrogen at 3 MPa (75% of anesthesia threshold) with differential pulse voltammetry have demonstrated a decrease in dopamine (DA) release by neurons originated from the substantia nigra pars compacta (SNc). Such a decrease is found also with compressed argon, which is more narcotic than nitrogen and with the anesthetic gas nitrous oxide. Inversely, compressed helium with its very low narcotic potency induces DA increase. Microdialysis studies in the striatum have indicated that nitrogen also induces a decrease of glutamate concentration. Nitrogen pressure did not modify NMDA glutamate receptor activities in SNc or striatum but enhanced GABAA receptors activities in SNc. Repetitive exposures to nitrogen narcosis suppressed the DA decrease and induced an increase. This fact and the lack of improvement of motor disturbances did not support the hypothesis of a physiological adaptation. The desensitization of the GABAA receptors on DA cells during recurrent exposures and the parallel long-lasting decrease of glutamate coupled to the increase in NMDA receptor sensitivity suggest a nitrogen neurotoxicity or addiction induced by recurrent exposures. The differential changes produced by inert gases indifferent neurotransmitter receptors would support the binding protein theory.
Asunto(s)
Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Narcosis por Gas Inerte/metabolismo , Membrana Dobles de Lípidos/metabolismo , Sustancia Negra/metabolismo , Adaptación Fisiológica , Anestésicos/metabolismo , Anestésicos/farmacología , Animales , Anexina A5/metabolismo , Presión Atmosférica , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/fisiología , Cristalografía/métodos , Dopamina/análisis , Ácido Glutámico/metabolismo , Helio/metabolismo , Helio/farmacología , Humanos , Hidrógeno/metabolismo , Hidrógeno/farmacología , Narcosis por Gas Inerte/etiología , Narcosis por Gas Inerte/fisiopatología , Proteínas de la Membrana/metabolismo , N-Metilaspartato/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Nitrógeno/metabolismo , Nitrógeno/farmacología , Ratas , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Sustancia Negra/efectos de los fármacos , Urato Oxidasa/metabolismoRESUMEN
The cytological location of ion channel antagonist-binding sites was studied in sunflower protoplasts using the fluorescent probes DM-Bodipy-PAA and DM-Bodipy-DHP. The binding specificity of the probes was established by competition experiments with Bepridil, phenylalkylamine (Verapamil) and dihydropyridine (Nifedipine) which are known as calcium and potassium channel antagonists. Quantitative image analysis of the fluorescence emitted by the protoplasts showed the existence of interactions between PAA- and DHP-binding sites. Moreover, studies on the cytolocalization of the PAA receptors by confocal imaging showed that in freshly isolated protoplasts, DM-Bodipy-PAA binds exclusively at sites located in the cortical region of the cell.
Asunto(s)
Colorantes Fluorescentes/metabolismo , Helianthus/metabolismo , Canales Iónicos/antagonistas & inhibidores , Sitios de Unión , Compuestos de Boro , Bloqueadores de los Canales de Calcio/metabolismo , Dimetilsulfóxido , Microscopía Confocal , Microscopía Fluorescente , Nifedipino/metabolismo , Protoplastos , Espectrometría de Fluorescencia , Verapamilo/metabolismoRESUMEN
We have investigated perforin and granzyme B expression in graft-infiltrating lymphocytes of patients who underwent heart transplantation. Those proteins are commonly present in the cytoplasmic granules of cytotoxic T lymphocytes and are released upon effector-target cell interaction. From 28 patients 103 endomyocardial biopsies were obtained and examined by histology and immunocytochemical analysis using relevant monoclonal antibodies. We found that "high" biopsy histological grades were associated with perforin and granzyme B expression in graft-infiltrating lymphocytes of patients with acute severe rejection crisis. In contrast, these markers were not detected in patients without rejection or during graft stabilization. Interestingly, in patients with mild rejection and "low" histological grades, two groups could be distinguished with a differential expression of the two intracytoplasmic proteins. The presence of perforin and granzyme B-expressing cells was found to be predictive of rapid progression to severe rejection, so that this situation required additional treatment; in contrast, their absence seemed to correlate with a good graft outcome without additional treatment. Moreover, perforin and granzyme B expression seemed to be down-regulated by immunosuppressive drugs, which coincided with graft stabilization. In conclusion, our data suggest that detection of granzyme B and perforin in graft-infiltrating lymphocytes might be helpful for routinely monitoring heart transplant patients.