RESUMO
Ghrelin and agonists of its receptor GHS-R1a are potential substances for the treatment of cachexia. In the present study, we investigated the acute and long term effects of the GHS R1a agonist JMV 1843 (H Aib-DTrp-D-gTrp-CHO) on food intake, body weight and metabolic parameters in lean C57BL/6 male mice. Additionally, we examined stability of JMV 1843 in mouse blood serum. A single subcutaneous injection of JMV 1843 (0.01-10 mg/kg) increased food intake in fed mice in a dose-dependent manner, up to 5-times relative to the saline-treated group (ED(50)=1.94 mg/kg at 250 min). JMV 1843 was stable in mouse serum in vitro for 24 h, but was mostly eliminated from mouse blood after 2 h in vivo. Ten days of treatment with JMV 1843 (subcutaneous administration, 10 or 20 mg/kg/day) significantly increased food intake, body weight and mRNA expression of the orexigenic neuropeptide Y and agouti-related peptide in the medial basal hypothalamus and decreased the expression of uncoupling protein 1 in brown adipose tissue. Our data suggest that JMV 1843 could have possible future uses in the treatment of cachexia.
Assuntos
Proteína Relacionada com Agouti/metabolismo , Estimulantes do Apetite/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Grelina/agonistas , Hipotálamo/efeitos dos fármacos , Neuropeptídeo Y/metabolismo , Oligopeptídeos/farmacologia , Aumento de Peso/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Proteína Relacionada com Agouti/genética , Animais , Estimulantes do Apetite/administração & dosagem , Estimulantes do Apetite/farmacocinética , Relação Dose-Resposta a Droga , Grelina/metabolismo , Hipotálamo/metabolismo , Indóis , Injeções Subcutâneas , Canais Iônicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Neuropeptídeo Y/genética , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacocinética , RNA Mensageiro/metabolismo , Receptores de Grelina/agonistas , Receptores de Grelina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triptofano/análogos & derivados , Proteína Desacopladora 1 , Regulação para CimaRESUMO
By nature, defensive behavior is risky. In social insects, such behavior is more likely to occur in individuals whose potential for other tasks is diminished. We show that workers of the termite Neocapritermes taracua develop an exceptional two-component suicidal apparatus consisting of copper-containing protein crystals, stored in external pouches, and internal salivary glands. During aggressive encounters, their bodies rupture, and the crystals react with the salivary gland secretion to produce a toxic droplet. Both the amount of defensive substances and the readiness to explode increase with workers' age, as their food-collecting ability declines.