RESUMEN
We previously demonstrated that the peptidergic neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP) affects the autonomic system and contributes to the control of metabolic and cardiovascular functions. Previous studies have demonstrated the importance of centrally-mediated sympathetic effects of leptin for obesity-related hypertension. Here we tested whether PACAP signaling in the brain is implicated in leptin-induced sympathetic excitation and appetite suppression. In anesthetized mice, intracerebroventricular (ICV) pre-treatment with PACAP6-38, an antagonist of the PACAP receptors (PAC1-R and VPAC2), inhibited the increase in white adipose tissue sympathetic nerve activity (WAT-SNA) produced by ICV leptin (2µg). In contrast, leptin-induced stimulation of renal sympathetic nerve activity (RSNA) was not affected by ICV pre-treatment with PACAP6-38. Moreover, in PACAP-deficient (Adcyap1-/-) mice, ICV leptin-induced WAT-SNA increase was impaired, whereas RSNA response was preserved. The reductions in food intake and body weight evoked by ICV leptin were attenuated in Adcyap1-/- mice. Our data suggest that hypothalamic PACAP signaling plays a key role in the control by leptin of feeding behavior and lipocatabolic sympathetic outflow, but spares the renal sympathetic traffic.
Asunto(s)
Tejido Adiposo Blanco/efectos de los fármacos , Riñón/efectos de los fármacos , Leptina/farmacología , Fragmentos de Péptidos/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Tejido Adiposo Blanco/inervación , Tejido Adiposo Blanco/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Inyecciones Intraventriculares , Riñón/inervación , Riñón/metabolismo , Masculino , Ratones , Ratones Noqueados , Especificidad de Órganos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/genética , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/metabolismo , Sistema Nervioso Simpático/fisiologíaRESUMEN
BACKGROUND: Various skin functions are affected by stress. We have previously shown that odorant inhalation can regulate skin immune reactions. OBJECTIVES: To test the hypothesis that certain odorants can mitigate the effects of stress on skin immune reactions. METHODS: Contact hypersensitivity (CH) reactions were elicited in C57BL/6 mice. Mice were subjected to immobilization stress and were exposed to odorants for 2 days. Epidermal sheets were stained for I-A antigens and analysed by confocal laser scanning microscopy. Serum corticosterone levels were assayed by radioimmunoassay. RESULTS: Exposure of mice to 1,3-dimethoxy-5-methylbenzene (DMMB) had no effect on the intact CH reaction, but it upregulated the reaction suppressed by immobilization stress. Other odorants, including terpinyl acetate and valerian oil, had minor effects on the CH reaction. Suppression of I-A-positive cells was prevented by DMMB inhalation. Valerian oil, but not DMMB, downregulated stress-induced plasma corticosterone levels. CONCLUSIONS: Results suggest that odorant inhalation modulates various physiological pathways, some of which result in regulation of skin function.
Asunto(s)
Dermatitis por Contacto/prevención & control , Tolerancia Inmunológica/efectos de los fármacos , Azul de Metileno/análogos & derivados , Odorantes , Estrés Fisiológico/inmunología , Animales , Corticosterona/sangre , Dermatitis por Contacto/sangre , Dermatitis por Contacto/inmunología , Femenino , Inmovilización , Células de Langerhans/efectos de los fármacos , Células de Langerhans/inmunología , Azul de Metileno/farmacología , Ratones , Ratones Endogámicos C57BL , Cloruro de Picrilo , Aceites de Plantas/farmacología , Terpenos/farmacología , ValerianaRESUMEN
In our previous experiments on animals evidence was found that citrus fragrance can restore the stress-induced immunosuppression, suggesting that citrus fragrance may have an effect on restoring the homeostatic balance. Since a dysregulation of the neuroendocrine and immune function is thought to be associated with psychosomatic or psychiatric disorders an attempt was made to restore their mental health by stimulation of one of the sensory systems. Fragrance (citrus was our choice) which comforts through stimulation of the olfactory system was applied to depressive patients. It was given to 12 depressive subjects and the results indicated that the doses of antidepressants necessary for the treatment of depression could be markedly reduced. The treatment with citrus fragrance normalized neuroendocrine hormone levels and immune function and was rather more effective than antidepressants.