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1.
J Parasitol ; 94(4): 771-9, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18576774

RESUMO

3',5'-Cyclic guanosine monophosphate (cGMP), a well-known intracellular second messenger, is released to the intestinal lumen by the tapeworm, Hymenolepis diminuta. Enzyme-linked immunosorbent assay analysis of tapeworm conditioned media shows that cGMP is released at a constant rate. Multidrug resistant (MDR) proteins are efflux transporters for cyclic nucleotides. Two MDR inhibitors, niflumic acid and zaprinast, inhibit cGMP secretion by tapeworms and change the cGMP localization within the tapeworm tegument, as assessed by immunochemistry. cGMP, normally present throughout the tapeworm tegumental cytoplasm, is absent from the outer cytoplasmic band upon treatment with inhibitors. Inhibition of cGMP secretion by colchicine indicates that cGMP secretion is cytoskeleton dependent. Binding studies of [3H]cGMP to ileal segments of intestine demonstrate 2 saturable, reversible, and high-affinity binding sites. These studies demonstrate that cGMP is secreted from the cestode via a cytoskeleton-dependent mechanism and MDR efflux transporters. In addition, cGMP reaching the intestinal lumen can bind to the mucosa via receptors for cGMP. These data, combined with earlier observations of cGMP altering intestinal motility and slowing lumenal transit, indicate that tapeworms alter the physiology of the host digestive process via the secretion and binding of extracellular cGMP to lumenal receptors in the host intestine.


Assuntos
GMP Cíclico/fisiologia , Hymenolepis diminuta/metabolismo , Íleo/metabolismo , Animais , Colchicina/farmacologia , GMP Cíclico/antagonistas & inibidores , GMP Cíclico/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Hymenolepis diminuta/efeitos dos fármacos , Íleo/parasitologia , Imuno-Histoquímica , Masculino , Ácido Niflúmico/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Purinonas/farmacologia , Ratos , Ratos Sprague-Dawley , Moduladores de Tubulina/farmacologia
2.
Neurosci Lett ; 392(3): 187-92, 2006 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-16278044

RESUMO

Atrial natriuretic peptide-(1-28) (ANP), brain natriuretic peptide-(1-32) (BNP) and C-Type natriuretic polypeptide (CNP) occur in the brain, are concentrated in the anteroventral area of the third cerebral ventricle and participate in the regulation of body fluid homeostasis. The ventricles of the mammalian brain are lined by a continuous monolayered epithelium of polyciliated ependymal cells. In the adult rat, the ependymocytes continue to express the intermediate filament vimentin, but do not contain glial fibrillary acidic protein. Ependymal functions are poorly understood, but may extend to osmoregulation and volume sensing. Ependymal cells possess receptors for the natriuretic peptides, and in cell culture respond to them with an increase in their cyclic GMP content. In this study, a cyclic GMP-specific antibody was employed together with an ex vivo brain slice system to assess the ependymal response to ANP, BNP and CNP under close to life-like conditions. While ANP in concentrations of 0.1 nM and 1 nM had no effect, at concentrations of 10nM and 100 nM it increased ependymal cyclic GMP levels in a concentration-dependent manner. The other natriuretic peptides BNP, and CNP, also increased the cyclic GMP content of ependymocytes, while nitric oxide (NO) donors had no effect. However, in contrast to the natriuretic peptides, the NO donors elevated the level of cyclic GMP in the brain parenchyma below the ependymal layer.


Assuntos
Encéfalo/citologia , GMP Cíclico/metabolismo , Epêndima/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Peptídeos Natriuréticos/farmacologia , Animais , Relação Dose-Resposta a Droga , Epêndima/enzimologia , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica/métodos , Técnicas In Vitro , Peptídeo Natriurético Encefálico/farmacologia , Peptídeo Natriurético Tipo C/farmacologia , Peptídeos Natriuréticos/classificação , Doadores de Óxido Nítrico/farmacologia , Ratos
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