RESUMO
The effects of cholecystokinin (CCK-8) and the CCK receptor antagonist proglumide, on antinociception induced by local peripheral (subcutaneous) injected morphine in non-diabetic (ND) and streptozotocin-induced diabetic (D) rats, were examined by means of the formalin test. Morphine induced dose-dependent antinociception both in ND and D rats. However, in D rats, antinociceptive morphine potency was about twofold less than in ND rats. Pre-treatment with CCK-8 abolished the antinociceptive effect of morphine in a dose-dependent manner in both groups of rats. Additionally, proglumide enhanced the antinociceptive effect induced by all doses of morphine tested. Both CCK-8 and proglumide had no effect on flinching behaviour when given alone to ND rats. Unlike ND rats, in D rats proglumide produced dose-dependent antinociception and CCK-8 enhanced formalin-evoked flinches, as observed during the second phase of the test. In conclusion, our data show a decrease in peripheral antinociceptive potency of morphine when diabetes was present. Additionally, peripheral CCK plays an antagonic role to the peripheral antinociceptive effect of morphine, additional to the well known CCK/morphine interaction at spinal and supraspinal level.
Assuntos
Colecistocinina/metabolismo , Morfina/uso terapêutico , Entorpecentes/uso terapêutico , Neuralgia/tratamento farmacológico , Animais , Área Sob a Curva , Colecistocinina/administração & dosagem , Colecistocinina/antagonistas & inibidores , Diabetes Mellitus Experimental/complicações , Relação Dose-Resposta a Droga , Interações Medicamentosas , Formaldeído/efeitos adversos , Masculino , Neuralgia/etiologia , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Proglumida/administração & dosagem , Ratos , Ratos WistarRESUMO
The Entamoeba histolytica mutant BG-3 has several altered cytoskeletal properties, including the distribution of actin and certain surface characteristics such as osmolarity and electrophoretic mobility. By Western blot analysis and assays for cell adhesion to collagen, we demonstrate that mutant BG-3 shows an increase in the phosphorylation levels of protein kinases that participate in proliferation, adhesion and migration, such as focal adhesion kinase and MAP kinase (Erk2), and that it has also altered its capacity of binding to collagen type I. These results indicate that E. histolytica cytoskeleton integrity plays an important role in adhesion and thus invasion of the host.
Assuntos
Citoesqueleto/fisiologia , Entamoeba histolytica/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Tirosina Quinases/metabolismo , Animais , Adesão Celular/fisiologia , Colágeno Tipo I/metabolismo , Entamoeba histolytica/genética , Entamoeba histolytica/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/química , Proteína-Tirosina Quinases de Adesão Focal , Mutação , Fosforilação , Proteínas Tirosina Quinases/químicaRESUMO
The interaction of Entamoeba histolytica trophozoites with collagen type I and calcium induces a membrane to nuclei signaling. The transduction pathways involved in such phenomena are still poorly understood. Using a combination of immunoprecipitation assays, Western immunoblot analysis, electrophoretic mobility shift assays and immunocytochemistry we demonstrate here the expression, tyrosine phosphorylation, nuclear translocation and DNA binding of two members of the signal transducers and activators of transcription family of inducible transcription factors in the protozoan parasite E. histolytica. These results support the notion that the interaction of the extracellular matrix components with the parasite turns on a genetic program that facilitates the invasion of the host.