Membrane-delimited proteolytic regulation of opioid receptors.

Prolonged exposure of opioid receptors to agonists leads to their regulation by the classical process of clathrin-dependent internalization, followed by their intracellular degradation (down regulation). We have previously shown that the opioid agonist etorphine induced an additional process of down regulation of mu-opioid receptors (MOR) that occurred in intact MOR-transfected HEK-293 cells, as well as in isolated membranes. In the present study we show that etorphine similarly down regulated rat kappa-opioid receptors (KORs), which do not undergo the classical process of internalization and down regulation. This process was resistant to inhibitors of clathrin-coated pit formation (hypertonic sucrose, mono-dansyl-cadaverine) and was mainly mediated by membranous serine- and amino-peptidases. We further show that various opioid ligands, besides etorphine, induced down regulation of either KOR or MOR in isolated membranes. The ability of the various opioid ligands to induce membrane-delimited KOR or MOR down regulation did not correlate to their classical pharmacological profile, suggesting functional selectivity of the effect. Levorphanol, but not its stereoisomer dextrophan, induced membrane-delimited down regulation of both KOR and MOR, indicating that stereoselective binding to the receptor was necessary to initiate the process. Our findings that this proteolytic regulation of opioid receptors occurs not only in isolated membranes but also in intact cells and that it occurs even when the receptors are resistant to the conventional process of down regulation indicate its possible physiological role in the regulation of opioid activity.

Factors influencing weight changes in callitrichids at the Bronx Zoo.

Callitrichids are small monkeys with high metabolic rates who appear to be susceptible to spontaneous diseases and possibly to environmental changes creating challenges in maintaining them in captivity. This study investigates whether life events (i.e. medical, social and housing changes) can influence weight. In previous research, body mass has been shown to be correlated with periods of illness, group composition changes and stress. Weights of 56 individual callitrichid monkeys (20 marmosets, 26 tamarins and 11 lion tamarins) at the WCS's Bronx Zoo were examined over approximately 2½ years. Weight fluctuations were scored based on 5%, 10% and 1 standard deviation criteria during periods of medical (illness and injury), social (introductions and separations), housing (movement within or between buildings) events and during periods when no-events occurred. Additionally, weights were examined for 3 months before and after periods of illness to look for trends in weight changes for 47 medical events (14 marmosets, 21 tamarins and 12 lion tamarins). Moreover, in five alloparenting males (four tamarins and one lion tamarin), weights were examined to determine if weight loss occurred after births as observed in earlier studies. The results show that a 5% and 1SD criterion may be too sensitive a criterion. We therefore deemed that a 10% weight loss may be the best criterion. For marmosets, a 10% weight loss occurred in association with all events. For tamarins, weight loss occurred with housing events. In lion tamarins, weight loss was observed with medical events. No significant weight loss was observed in alloparenting males.

La biografía del niño relatada por los padres: ¿fuente u obstáculo para la interpretación? / The parent’s account of the child’s life story, source or hindrance for interpretations?

A partir de viñetas clínicas planteamos algunas reflexiones sobre el estatuto que la biografía del niño relatada por sus padres tiene en la mente del analista durante el trabajo analítico con su paciente; y su incidencia en la formulación de la interpretación en la sesión. Este trabajo transita entre dos posturas encontradas: aquella que plantea que la clínica de niños es imposible si no se atiende el discurso parental; aquella que plantea como posible el análisis de niños prescindiendo de la narrativa de los padres