RESUMO
When brothers Jamie and Glen Selby, aged 5 and 7, arrived at the Shriners Burns Institute in Denver, Colorado, in July 1983, more than 97% of their skin had been destroyed by a fire they had accidentally started while playing in an abandoned house. The boys were so badly burned that their outlook was grim-a 6-year-old friend who was also in the fire died from his injuries?but Jamie and Glen were lucky. Not only did they survive, but they were also some of the first patients to benefit from a new burn treatment nicknamed test-tube skin.
Assuntos
Pesquisa Biomédica , Queimaduras , Animais , Queimaduras/diagnóstico , Queimaduras/fisiopatologia , Queimaduras/terapia , Cicatriz/prevenção & controle , Terapia por Estimulação Elétrica , Humanos , Camundongos , Monitorização Fisiológica , Curativos Oclusivos , Dor/prevenção & controle , Pele Artificial , CicatrizaçãoRESUMO
The receptor subtypes that mediate the effects of neuropeptide Y (NPY) on food intake have not been clearly defined. The NPY Y4 receptor has been identified recently as a potential mediator of the regulation of food intake. The purpose of the present study was to characterize the central site of action of the Y4 receptor using a combination of neuroanatomical and physiological approaches. Using immunocytochemistry, Y4-like immunoreactivity was found to be colocalized with orexin cell bodies in the lateral hypothalamic area (LHA) and orexin fibers throughout the brain. In situ hybridization confirmed the expression of Y4 mRNA in orexin neurons. To determine the functional interaction between Y4 receptors and orexin neurons, we examined the effects of rat pancreatic polypeptide (rPP), a Y4-selective ligand, or NPY, a nonselective ligand, administered directly into the LHA on the stimulation of food and water intake and c-Fos expression. Both rPP and NPY significantly increased food and water intake when they were administered into the LHA, although NPY was a more potent stimulator of food intake. Furthermore, both NPY and rPP significantly stimulated c-Fos expression in the LHA. However, whereas rPP stimulated c-Fos expression in orexin neurons, NPY did not. Neither rPP nor NPY stimulated c-Fos in melanin-concentrating hormone neurons, but both activated neurons of an unknown phenotype in the LHA. These results suggest that a functional Y4 receptor is expressed on orexin neurons and that these neurons are activated in response to a ligand with high affinity for the Y4 receptor (rPP). Although these data suggest a role for central Y4 receptors, the endogenous ligand for this receptor has yet to be clearly established.