Publications (88) View all
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Article: Characterization of rat heart alkaline phosphatase isoenzymes and modulation of activity.
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ABSTRACT: Alkaline phosphatase (ALP) is important in calcification and its expression seems to be associated with the inflammatory process. We investigated the in vitro acute effects of compounds used for the prevention or treatment of cardiovascular diseases on total ALP activity from male Wistar rat heart homogenate. ALP activity was determined by quantifying, at 410 nm, the p-nitrophenol released from p-nitrophenylphosphate (substrate in Tris buffer, pH 10.4). Using specific inhibitors of ALP activity and the reverse transcription-polymerase chain reaction, we showed that the rat heart had high ALP activity (31.73 +/- 3.43 nmol p-nitrophenol.mg protein-1.min-1): mainly tissue-nonspecific ALP but also tissue-specific intestinal ALP type II. Both ALP isoenzymes presented myocardial localization (striated pattern) by immunofluorescence. ALP was inhibited a) strongly by 0.5 mM levamisole, 2 mM theophylline and 2 mM aspirin (91, 77 and 84%, respectively) and b) less strongly by 2 mM L-phenylalanine, 100 mL polyphenol-rich beverages and 0.5 mM progesterone (24, 21 to 29 and 11%, respectively). beta-estradiol and caffeine (0.5 and 2 mM) had no effect; 0.5 mM simvastatin and 2 mM atenolol activated ALP (32 and 36%, respectively). Propranolol (2 mM) tended to activate ALP activity and corticosterone activated (18%) and inhibited (13%) (0.5 and 2 mM, respectively). We report, for the first time, that the rat heart expresses intestinal ALP type II and has high total ALP activity. ALP activity was inhibited by compounds used in the prevention of cardiovascular pathology. ALP manipulation in vivo may constitute an additional target for intervention in cardiovascular diseases.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 08/2008; 41(7):600-9. · 1.08 Impact Factor -
Article: Short-term exposure to somatostatin or muscarinic agonists reduce acetylcholine-induced 3H-MPP+ release from bovine adrenal medullary cells.
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ABSTRACT: The aim of this work was to investigate the effect of a short-term exposure to somatostatin (SS), its receptors (SSTR) selective agonists as well as muscarinic receptors agonists upon acetylcholine-induced release of (3)H-MPP(+ )from bovine adrenal medullary cells. Acetylcholine (ACH, 100, 500 microM) was found to increase the release of (3)H-MPP(+ )by these cells (to 175 and 171% of basal release, respectively). ACH-elicited (3)H-MPP(+) release was significantly reduced by hexamethonium (100 microM) and atropine (100 microM), selective nicotinic and muscarinic antagonists, respectively. Previous exposure to any of two muscarinic agonists, oxotremorine or pilocarpine, led to a significant reduction of (3)H-MPP(+) release in response to 100 microM ACH, to about a maximum of 51% and 78% of control, respectively. Somatostatin (SS, 0.01-0.1 microM), previously applied to the preparation, depressed ACH-elicited (3)H-MPP(+ )release by 25-27%, but only when a 500 microM ACH concentration was used. The inhibition exerted by SS upon ACH-evoked (3)H-MPP(+) release appeared to be mediated by its SSTR: (1) SSTR2, 3 and 4 subtype agonists mimicked the effects seen with SS, and (2) the SSTR non-selective antagonist, cyclo-SS, counteracted the SS inhibitory effect. When SS was tested in the presence of any of the muscarinic agonists, oxotremorine or pilocarpine, its inhibitory effect on 500 microM ACH-induced (3)H-MPP(+) release was no longer detectable. These results, showing a somewhat similar effect of short-term exposure to SS and muscarinic agonists over ACH-induced release of (3)H-MPP(+), as well as the loss of effect of SS by the presence of the muscarinic agonists, suggest that these compounds may share signalling pathways.Journal of Biomedical Science 06/2007; 14(3):347-55. · 2.01 Impact Factor -
Article: Recent advances on the importance of the serotonin transporter SERT in the rat intestine.
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ABSTRACT: Serotonin (5-HT) is present in high concentration in enterochromaffin cells throughout the gastrointestinal tract, where it plays a very important role, being involved, e.g., in peristaltic and secretory reflexes in response to chemical or mechanical stimuli of the gut. Intestinal 5-HT is inactivated by metabolic degradation after cellular uptake mediated by the serotonin transporter SERT. This mini-review summarizes some recent data obtained by our group on the importance, regional distribution and cell membrane localization of SERT in the rat intestine. From our results, we conclude that SERT is located both at the apical and basolateral cell membranes of intestinal epithelial cells in the three intestinal regions studied: jejunum, ileum and colon. Moreover, we also conclude that inhibition of SERT causes an increase in transmural transport of 5-HT in these three intestinal segments, probably because it increases the extracellular concentration of 5-HT. Consequently, SERT inhibition will be able to cause an increase in the physiological responses of the tissue to this amine. The repercussions of this phenomenon are discussed.Pharmacological Research 09/2006; 54(2):73-6. · 4.44 Impact Factor -
Article: Modulation of MPP+ uptake by tea and some of its components in Caco-2 cells.
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ABSTRACT: The entry of most xeno/endobiotics into the organism is limited by their intestinal absorption. The interference of certain foods with the therapeutic efficacy of drugs or with chemical toxicity is becoming evident and growing attention is being given to these subjects. The aim of this work was to study the effect of green tea (GT) and black tea (BT), as well as some of their components, on the transport of organic cation molecules. For this purpose, 3H-MPP+ (radiolabeled 1-methyl-4-phenylpyridinium) was used as a model organic cation and Caco-2 cells were used as an intestinal epithelial model. Our results showed that both GT and BT significantly increased 3H-MPP+ absorption in these cells. Additionally, we studied the effect of epigallocatechin-3-gallate (EGCG), myricetin, caffeine, and theophylline. Whereas EGCG (2 mM) increased, myricetin (50 microM) and caffeine (1 mM) decreased, and theophylline (1 mM) had no effect on the uptake of 3H-MPP+ into Caco-2 cells. When GT was supplemented with caffeine or theophylline, we observed a partial loss of its effect. When BT was supplemented with EGCG, its ability to increase 3H-MPP+ uptake was much more pronounced than that observed with BT alone. In conclusion, this study showed that GT and BT might interfere with the absorption of the model organic cation MPP+ by the intestinal epithelium. Since important compounds are organic cations, the consequences of this interference may have an impact on human health. Although this constitutes only preliminary work and further studies are needed, tea should be included in the growing list of foodstuffs that have the potential to be involved in food-drug interactions.Archiv für Experimentelle Pathologie und Pharmakologie 09/2005; 372(2):147-52. · 2.65 Impact Factor -
Article: Intestinal uptake of MPP+ is differently affected by red and white wine.
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ABSTRACT: It is becoming increasingly evident that ingested products, such as wine, may have profound effects on the therapeutic efficacy of certain drugs. As various xeno- and endobiotics are organic cations, the purpose of our study was to examine the modulation of organic cations intestinal apical uptake by red (RW) and white wine (WW). For this purpose, we used RW, WW, the same alcohol-free wines, phenolic compounds and ethanol. The uptake of the organic cation 1-methyl-4-phenylpyridinium (MPP+) was evaluated in Caco-2 cells, an intestinal epithelial cell model. RW and alcohol-free RW increased 3H-MPP+ apical uptake, although the effect of alcohol-free RW was less pronounced. On the other hand, WW and alcohol-free WW decreased the organic cation uptake but the effect of alcohol-free WW was more pronounced. Our results show that the total content in phenolic compounds was 7 times higher, and the dialysis index was about 4 times higher in RW compared to WW. Ethanol, in the same concentration found in wine, caused a significant decrease in 3H-MPP+ apical uptake. The solution containing high molecular weight compounds from dialyzed RW increased 3H-MPP+ apical uptake. In conclusion, the results suggest that RW may increase and WW may reduce the intestinal absorption of organic cations present in the diet, such as drugs or vitamins (e.g. thiamine and riboflavin). As ethanol alone decreased the uptake of MPP+, and alcohol-free RW and WW had a lower potency than intact wine upon the transport, the presence of ethanol is probably important for the solubilisation/bioavailability of the components endowed with the transport modulating activity.Life Sciences 05/2005; 76(21):2483-96. · 2.53 Impact Factor
