RESUMO
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Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Dermatomiosite/diagnóstico , Dermatomiosite/patologia , Neoplasias Esplênicas/etiologia , Imunoglobulinas/administração & dosagem , Eritema/complicaçõesAssuntos
Dermatomiosite/diagnóstico , Linfoma não Hodgkin/complicações , Síndromes Paraneoplásicas/diagnóstico , Neoplasias Esplênicas/complicações , Corticosteroides/uso terapêutico , Terapia Combinada , Transtornos de Deglutição/etiologia , Dermatomiosite/etiologia , Dermatomiosite/terapia , Erros de Diagnóstico , Dermatoses Faciais/diagnóstico , Dermatoses Faciais/etiologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/terapia , Urticária/diagnósticoRESUMO
Adenosine is readily available to the glandular epithelium of the stomach. Formed continuously in intracellular and extracellular locations, it is notably produced from ATP released in enteric cotransmission. Adenosine analogs modulate chloride secretion in gastric glands and activate acid secretion in isolated parietal cells through A2B adenosine receptor (A2BR) binding. A functional link between surface A2BR and adenosine deaminase (ADA) was found in parietal cells, but whether this connection is a general feature of gastric mucosa cells is unknown. Here we examine whether A2BR is expressed at the membrane of histamine-producing enterochromaffin-like (ECL) cells, the major endocrine cell type in the oxyntic mucosa, and if so, whether it has a vicinity relationship with ADA. We used a highly homogeneous population of rabbit ECL cells (size 7.5-10 µm) after purification by elutriation centrifugation. The surface expression of A2BR and ADA proteins was assessed by flow cytometry and confocal microscopy. Our findings demonstrate that A2BR and ADA are partially coexpressed at the gastric ECL cell surface and that A2BR is functional, with regard to binding of adenosine analogs and adenylate cyclase activation. The physiological relevance of A2BR and ADA association in regulating histamine release is yet to be explained.
Assuntos
Adenosina Desaminase/genética , Celulas Tipo Enterocromafim/metabolismo , Mucosa Gástrica/citologia , Mucosa Gástrica/metabolismo , Expressão Gênica , Receptor A2B de Adenosina/genética , Adenosina Desaminase/metabolismo , Animais , Biomarcadores , Citometria de Fluxo , Coelhos , Receptor A2B de Adenosina/metabolismoRESUMO
Adenosine modulates different functional activities in many cells of the gastrointestinal tract; some of them are believed to be mediated by interaction with its four G protein-coupled receptors. The renewed interest in the adenosine A2B receptor (A2BR) subtype can be traced by studies in which the introduction of new genetic and chemical tools has widened the pharmacological and structural knowledge of this receptor as well as its potential therapeutic use in cancer and inflammation- or hypoxia-related pathologies. In the acid-secreting parietal cells of the gastric mucosa, the use of various radioligands for adenosine receptors suggested the presence of the A2 adenosine receptor subtype(s) on the cell surface. Recently, we confirmed A2BR expression in native, nontransformed parietal cells at rest by using flow cytometry and confocal microscopy. In this study, we show that A2BR is functional in primary rabbit gastric parietal cells, as indicated by the fact that agonist binding to A2BR increased adenylate cyclase activity and acid production. In addition, both acid production and radioligand binding of adenosine analogs to isolated cell membranes were potently blocked by selective A2BR antagonists, whereas ligands for A1, A2A, and A3 adenosine receptors failed to abolish activation. We conclude that rabbit gastric parietal cells possess functional A2BR proteins that are coupled to Gs and stimulate HCl production upon activation. Whether adenosine- and A2BR-mediated functional responses play a role in human gastric pathophysiology is yet to be elucidated.