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Abstract(s)
Os recetores olfativos (ORs) são proteínas transmembranares, associadas à proteína G e que funcionam, no epitélio olfativo, como quimiosensores para a deteção de odores. A capacidade do sistema olfativo para detetar um vasto universo de compostos químicos depende, em larga medida, do fato de existirem cerca de 1000 genes de ORs no genoma dos mamíferos. No epitélio olfativo, a informação sobre os odores, recebida por esta multiplicidade de ORs, é canalizada apenas por uma via de sinalização. Quando a molécula de odor se liga ao OR, este ativa um tipo específico de proteína G, a proteína G olfativa trimérica (Golf), a qual por sua vez ativa a isoforma olfativa da adenilato ciclase (AC3), resultando num aumento de Adenosina Monofosfato Cíclica (cAMP). Um dos alvos do cAMP é um canal catiónico que, quando aberto, permite um influxo de iões sódio (Na+) e iões cálcio (Ca2+) no cílio, resultando numa despolarização da célula. Tanto a AC3 como a Golf e o canal catiónico são constituintes obrigatórios da maquinaria olfativa. Já foram descritas algumas situações, em que os ORs têm funções quimiosensoriais, fora do epitélio olfativo nomeadamente no esperma, placenta e rim. Com este projeto, pretendeu-se saber se as vias de sinalização dos ORs são usadas pelas células intestinais de forma a responder a alterações no lúmen do trato gastrointestinal. O estudo da expressão a nível do mRNA, foi desenvolvido por RT-PCR e a análise da expressão das proteínas por Western Blotting e Imunohistoquímica. Os principais constituintes da via olfativa foram identificados no intestino: os ensaios de Western Blot e Imunohistoquímica mostraram a presença dos recetores olfativos (OR19, OR63, OR600, OR620/624 e OR1496), a adenilato ciclase tipo 3 (AC3) e a subunidade α da proteína G específica do olfato (Gαolf). Os estudos de RT-PCR, embora ainda em curso, mostraram a presença de mRNA de genes que codificam para recetores olfativos e para a Gαolf. Os resultados obtidos neste projeto experimental sugerem que a cascata de sinalização da transdução olfativa pode estar ativa no intestino, uma vez que as várias proteínas que a constituem se encontram expressas neste tecido. Esta via pode regular a motilidade do intestino e funcionar como um detetor de moléculas químicas solúveis que se encontrem no lúmen intestinal, induzindo respostas celulares de acordo com as necessidades fisiológicas.
Olfactory receptors (ORs) are transmembrane proteins associated with G protein involved in recognition and transduction of odorant stimuli. The ability of the olfactory system to detect a broad universe of chemical compounds depends largely on the fact that there are about 1000 genes in the ORs mammalian genome. In the olfactory epithelium, the information about odors, received by this plurality of ORs is channeled only through a signaling pathway. When the OR binds to the odor molecule, it activates a specific type of G protein, the specific olfactory trimeric G-protein (Golf), which in turn activates adenylate cyclase olfactory isoform (AC3), resulting in an increase in Adenosine Monophosphate Cyclic (cAMP). One of the targets of cAMP is a cation channel which, when opened, allows an influx of sodium ions (Na+ ) and calcium ions (Ca2+) in the cilia, resulting in depolarization of the cell. Both the AC3 as the Golf and the cationic channel are mandatory components in the olfactory machinery. Olfactory-like chemosensory signaling occurs outside the olfactory epithelium, in other tissues where it also monitors the composition of fluids, in particular sperm, placenta, and kidney. So, with this project, we sought to know whether the olfactory signaling pathways are used by intestinal cells to respond to changes in the lumen of the gastrointestinal tract. The RNA analysis was performed by conventional PCR, and protein analysis by Western Blotting and Immunohistochemistry. We found that major components of olfaction, including olfactory receptors (OR19, OR63, OR600, OR620/624 e OR1496), olfactory-related adenylate cyclase (AC3) and olfactory G protein (Gαolf), are expressed in the rat bowel. These results suggest that olfactory-like chemosensory pathway might be active in bowel and could function as regulator of intestine motility and as a detector of soluble chemical molecules in intestinal lumen, therefore inducing several cellular responses, according to physiological needs.
Olfactory receptors (ORs) are transmembrane proteins associated with G protein involved in recognition and transduction of odorant stimuli. The ability of the olfactory system to detect a broad universe of chemical compounds depends largely on the fact that there are about 1000 genes in the ORs mammalian genome. In the olfactory epithelium, the information about odors, received by this plurality of ORs is channeled only through a signaling pathway. When the OR binds to the odor molecule, it activates a specific type of G protein, the specific olfactory trimeric G-protein (Golf), which in turn activates adenylate cyclase olfactory isoform (AC3), resulting in an increase in Adenosine Monophosphate Cyclic (cAMP). One of the targets of cAMP is a cation channel which, when opened, allows an influx of sodium ions (Na+ ) and calcium ions (Ca2+) in the cilia, resulting in depolarization of the cell. Both the AC3 as the Golf and the cationic channel are mandatory components in the olfactory machinery. Olfactory-like chemosensory signaling occurs outside the olfactory epithelium, in other tissues where it also monitors the composition of fluids, in particular sperm, placenta, and kidney. So, with this project, we sought to know whether the olfactory signaling pathways are used by intestinal cells to respond to changes in the lumen of the gastrointestinal tract. The RNA analysis was performed by conventional PCR, and protein analysis by Western Blotting and Immunohistochemistry. We found that major components of olfaction, including olfactory receptors (OR19, OR63, OR600, OR620/624 e OR1496), olfactory-related adenylate cyclase (AC3) and olfactory G protein (Gαolf), are expressed in the rat bowel. These results suggest that olfactory-like chemosensory pathway might be active in bowel and could function as regulator of intestine motility and as a detector of soluble chemical molecules in intestinal lumen, therefore inducing several cellular responses, according to physiological needs.
Description
Keywords
Transdução olfativa Transdução olfativa - Instestino Receptores olfactivos AC3 (Adelinato Ciclase tipo 3)