RESUMO
Since we have previously shown a direct inhibitory effect of platelet-activating factor (PAF) on Cl reabsorption in the medullary thick ascending limb of Henle's loop (TAL), the aim of this study was to extend this effect to the whole TAL and to further investigate the signaling pathway involved. In microperfused cortical TALs, PAF significantly decreased Cl reabsorption by 50.3 +/- 6.5%. On the one hand, this effect was not modified in the presence of staurosporine and was not mimicked by phorbol ester; chelating cytosolic Ca by BAPTA/AM failed to suppress the inhibitory effect of PAF on Cl reabsorption; moreover, no significant increase in intracellular Ca concentration could be observed in the presence of PAF on isolated tubules. On the other hand, 8-bromo cyclic GMP mimicked the PAF effect on Cl reabsorption and prevented a further effect of this agent; the PAF effect was significantly reduced by H-8, a cyclic GMP-dependent protein kinase inhibitor; in medullary TALs, PAF significantly increased by twofold cyclic GMP content, an effect inhibited by the PAF antagonist BN 50730, whereas PAF did not significantly modify cAMP content in basal or stimulated conditions. Finally, inhibition of nitric oxide production by NAME or NMMA failed to prevent the effect of PAF on Cl reabsorption. It is concluded that the PAF-induced inhibition of Cl reabsorption in the TAL was mediated by cyclic GMP, likely independent of a nitric oxide synthesis.
Assuntos
Cloretos/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Medula Renal/fisiologia , Alça do Néfron/fisiologia , Fator de Ativação de Plaquetas/farmacologia , Aminoácido Oxirredutases/antagonistas & inibidores , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Cálcio/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Técnicas In Vitro , Isoquinolinas/farmacologia , Medula Renal/efeitos dos fármacos , Cinética , Alça do Néfron/efeitos dos fármacos , Masculino , Camundongos , NG-Nitroarginina Metil Éster , Óxido Nítrico Sintase , Nitroprussiato/farmacologia , Hormônio Paratireóideo/farmacologia , Proteína Quinase C/antagonistas & inibidores , Fatores de Tempo , Vasopressinas/farmacologia , ômega-N-MetilargininaRESUMO
Bifidobacteria, naturally present in the dominant colonic microbiota, represent up to 25% of the cultivable faecal bacteria in adults and 80% in infants. As probiotic agents, bifidobacteria have been studied for their efficacy in the prevention and treatment of a broad spectrum of animal and/or human gastrointestinal disorders, such as colonic transit disorders, intestinal infections, and colonic adenomas and cancer. The aim of this review is to focus on the gastrointestinal effects of bifidobacteria as probiotic agents in animal models and man. The traditional use of bifidobacteria in fermented dairy products and the GRAS ('Generally Recognised As Safe') status of certain strains attest to their safety. Some strains, especially Bifidobacterium animalis strain DN-173 010 which has long been used in fermented dairy products, show high gastrointestinal survival capacity and exhibit probiotic properties in the colon. Bifidobacteria are able to prevent or alleviate infectious diarrhoea through their effects on the immune system and resistance to colonization by pathogens. There is some experimental evidence that certain bifidobacteria may actually protect the host from carcinogenic activity of intestinal flora. Bifidobacteria may exert protective intestinal actions through various mechanisms, and represent promising advances in the fields of prophylaxis and therapy.
Assuntos
Bifidobacterium , Gastroenteropatias/prevenção & controle , Trato Gastrointestinal/microbiologia , Probióticos/uso terapêutico , Adulto , Proliferação de Células , Feminino , Trânsito Gastrointestinal , Humanos , Lactente , Masculino , Neoplasias/prevenção & controleRESUMO
Since, in the presence of ANF, urinary cGMP was shown to be of glomerular origin, a possible paracrine effect of luminal cGMP on the medullary thick ascending limb (mTAL) function was investigated. Net chloride reabsorption (JCl) was determined on isolated microperfused tubules from mouse kidney. Addition of 10(-6) M cGMP to the lumen significantly decreased JCl by 46.5 +/- 4.6%. A concentration-dependent decrease of the transepithelial voltage was observed, with a 10(-8) M threshold. Added to the bath, ANF (10(-7) M) as well as urodilatin (6 x 10(-8) M) decreased JCl by 29.8 +/- 3.9% and 36.9 +/- 5.1%, respectively, an effect reproduced by 8-bromo cGMP and associated with a significant increase in tubular cGMP content. The inhibitory effect of ANF was similar whether or not cGMP was present in the lumen. Furthermore, increasing intracellular cGMP content by 8-bromo cGMP did not prevent a further effect of luminal cGMP. Finally, H-8, which blocked the effect of ANF, urodilatin, and 8-bromo cGMP, failed to abolish the luminal cGMP-induced decrease of JCl, suggesting that this effect did not require a cGMP-dependent protein kinase activation. It is concluded that luminal cGMP inhibits the reabsorptive function of the mTAL through a pathway different from the intracellular cGMP production.