Possible autocrine enkephalin regulation of catecholamine release in human pheochromocytoma cells.

AIMS: Pheochromocytomas are catecholamine-secreting tumors that also synthesize and secrete several neuropeptides, including opioids. A negative regulation of catecholamine secretion by opioids has been postulated in chromaffin cells. However, results obtained so far are contradictory when referred to human pheochromocytomas. The aim of this study was to define the role of locally produced enkephalins on catecholamine release in human pheochromocytoma cells. MAIN METHODS: Cells obtained from eleven human pheochromocytomas of different genetic origins were cultured for 5 days. Cultures were maintained under basal condition or under enkephalin, dexamethasone and naloxone alone or in combination with enkephalin or dexamethasone-stimulated conditions. Catecholamine and enkephalin levels in the culture medium were measured by HPLC-ED and RIA respectively. KEY FINDINGS: Enkephalin induced a decrease in norepinephrine levels in all tumor cultures. Dexamethasone treatment, which increased enkephalin levels, also decreased catecholamine levels. On the other hand, the addition of naloxone to the cultures reverted to normal the inhibitory action exerted by enkephalin and dexamethasone treatments. SIGNIFICANCE: These results suggest the existence of an autocrine negative regulatory loop exerted by enkephalin on norepinephrine release in human pheochromocytoma cells.

Changes in Proenkephalin mRNA expression in forebrain areas after amphetamine-induced behavioural sensitization.

Acute and repeated psychostimulant administration induces a long-lasting enhanced behavioural response to a subsequent drug challenge, known as behavioural sensitization. This phenomenon involves persistent neurophysiological adaptations, which may lead to drug addiction. Brain dopaminergic pathways have been implicated as the main neurobiological substrates of behavioural sensitization, although other neurotransmitters and neuromodulators may also participate. In order to investigate a possible involvement of opioid systems in amphetamine (AMPH) behavioural sensitization, we studied the AMPH-induced changes in Proenkephalin (Pro-Enk) mRNA expression in forebrain areas in both drug-naïve and AMPH-sensitized rats. Male Sprague-Dawley rats were sensitized to AMPH by means of a single AMPH (1 mg/kg s.c.) injection and the same dose was injected 7 days later to assess the expression of sensitization. Pro-Enk mRNA levels were evaluated by in situ hybridization in coronal brain sections. AMPH injection induced an increase in Pro-Enk mRNA expression in the nucleus accumbens and the medial-posterior caudate-putamen in drug-naïve rats. Challenge with AMPH to rats injected 1 week earlier with AMPH induced motor sensitization and increased and decreased Pro-Enk mRNA expression in the prefrontal cortex and the anterior medial caudate-putamen, respectively. Our results suggest that alterations in cortical and striatal enkephalinergic systems could contribute to the expression of AMPH behavioural sensitization.

Breve introducción a la neuroinmunología / Brief introduction to the neuroimmunology

A partir de la década de los setentas se ha demostrado una importante dependencia direccional entre los sistemas inmune (SI) y el sistema nervioso central (SNC), con la intervención de mensajeros comunes. Las citocinas del SI son capaces de modular respuestas y procesos a nivel del SNC, mientras que los neurotransmisores y neuropéptidos pueden a su vez ejercer su efecto sobre grupos celulares especificos del SNC. Un grupo importante de estos péptidos es el de los opioides endógenos, como las endorfinas y las encefalinas. Las endorfinas alfa y beta tienen la capacidad de activar la quimiotaxis e influenciar la diferenciación y proliferación de linfocitos T y B. La ß-endorfina incrementa la actividad de las células natural killer (NK). La met-encefalina y la leu-encefalina desarrollan funciones de tipo inmunomodulador con respecto a la producción de anticuerpos (Acs) por las células plasmáticas. Incrementan la producción de Acs., pueden aumentar el número de leucocitos circulantes y la producción de interleucina-2 (IL-2). Una vía en el sistema neuroinmunológico es controlada por el eje-HPA (hipotálamo-pituitaria-adrenales, principal coordinador y regulador de las interacciones entre el sistema inmune, el SNC y el endocrino

Enkephalinase inhibition facilitates sexual behavior in the male rat but does not produce conditioned place preference.

The effects of two enkephalinase inhibitors, SCH 34826 and phospho-leu-phe, on male rat sexual behavior and conditioned place preference were evaluated. SCH 34826, administered intraperitoneally, reduced the ejaculation latency to both the first and second ejaculation at a dose of 30 mg/kg. This dose also reduced the first postejaculatory interval. No other effect was obtained with this drug. Phospho-leu-phe, administered intracerebroventricularly, increased mount and intromission latency at doses of 50 and 100 micrograms. A dose of 25 micrograms reduced the latency to the first ejaculation as well as the number of preejaculatory intromissions. The postejaculatory interval was also reduced at this dose. SCH 34826, 100 and 30 mg/kg, and phospho-leu-phe, 25 micrograms, had no effect in the conditioned place preference procedure. These observations seem to suggest that there is no functionally relevant tonic release of enkephalins. Therefore, the effects obtained on sexual behavior may indicate that enkephalins are released before and during the course of sexual activity. The function of such a release could be to facilitate ejaculatory mechanisms in the way found in the present studies. Previous work has shown that ejaculation-induced reward is opioid dependent, further supporting the hypothesis of opioid release during sexual activity. Taken together, these data suggest an important role for opioids, probably enkephalins, in the physiological control of sexual behavior.

[The central nervous system and neuroendocrine system in the regulation of the immune response]. / El sistema nervioso central y el sistema neuroendócrino en la regulación de la respuesta inmune.

There is at present a clear trend in the study of psychoneuroimmunoregulatory events. Different experimental models have demonstrated: a) the participation of stress, psychosocial factors and the central nervous system in the regulation of the immune response; b) an extensive innervation by the autonomic nervous system of the lymphatic organs; c) the presence of receptors for the neuroendocrine mediators in the mononuclear peripheral cells; d) the activity of neuropeptides, hormones and neurotransmitters in lymphocyte activation and function; e) the production of neuroendocrine substances by lymphocytes; f) the existence of feedback pathways in the immune system. In our laboratory we have contributed to these studies with the description of: a) the regulatory activity of different neuroendocrine substances on interferon-gamma production; b) the characterization of the immune regulation exercised by the muscarinic cholinergic system; c) the in vitro activity of the indoleamines, serotonin and melatonin on the immune response, and the production of these indoleamines by lymphocytes and monocytes, thus establishing a model of paracrine regulation.