Drugs online research references
Ren Physiol Biochem. 1993 Jul-Aug;16(4):157-66.
Transepithelial Ca2+ and Mg2+ transport in the cortical thick ascending limb of Henle's loop of the mouse is a voltage-dependent process.
Di Stefano A, Roinel N, de Rouffignac C, Wittner M.
Departement de Biologie Cellulaire et Moleculaire, CE Saclay, Gif-sur-Yvette, France.
The mechanisms responsible for transepithelial Ca2+ and Mg2+ in transport in the isolated perfused cortical thick ascending limb (cTAL) of Henle's loop of the mouse nephron were investigated by measuring transepithelial voltages (PDte) and transepithelial ion net fluxes (JNa, JCl, JK, JCa, JMg) by electron microprobe analysis. In the presence of furosemide (10(-4) mol.l-1, lumen) and diphenylamine-2-carboxylate (DPC, 10(-4) mol.l-1, bath), known inhibitors of NaCl reabsorption in the TAL, Ca2+ and Mg2+ reabsorption was completely inhibited. In the presence of furosemide, JCa fell from 0.75 +/- 0.07 to -0.08 +/- 0.09 pmol.min-1.mm-1 (n = 5), and JMg from 0.47 +/- 0.04 to -0.01 +/- 0.11 pmol.min-1.mm-1 (n = 5). In the presence of DPC, JCa fell from 0.57 +/- 0.08 to -0.07 +/- 0.11 pmol.min-1.mm-1 (n = 5), and JMg from 0.16 +/- 0.02 to -0.11 +/- 0.07 pmol.min-1.mm-1 (n = 5). With furosemide, inhibition of Ca2+ and Mg2+ transport was paralleled by a 93% inhibition of NaCl reabsorption, while in the presence of DPC there was a 60% reduction of NaCl reabsorption. These effects were fully reversed after removal of the inhibitors from the lumen or bath solutions. In the absence of active NaCl transport, a lumen-to-bath directed-NaCl gradient (lumen: 150 mM NaCl + furosemide, bath: 50 mM NaCl + 200 mM mannitol) generated a negative transepithelial dilution potential of -13.8 +/- 1.1 mV (n = 8) which induced a significant Ca2+ and Mg2+ secretion into the tubular lumen of -0.59 +/- 0.06 and -0.43 +/- 0.05 pmol.min-1.mm-1 (n = 8), respectively. A bath-to-lumen-directed NaCl gradient, on the other hand, (lumen: 50 mM NaCl + furosemide, bath: 150 mM NaCl) generated a positive transepithelial dilution potential of +15.9 +/- 0.6 mV (n = 7), inducing a significant Ca2+ and Mg2+ reabsorption of 0.62 +/- 0.08 and 0.38 +/- 0.07 pmol.min-1.mm-1 (n = 7), respectively. Linear regression analysis of individual Ca2+ and Mg2+ net flux data versus voltage indicated that JCa and JMg were highly correlated to PDte. In conclusion, these data indicate that transepithelial Ca2+ and Mg2+ reabsorption in the mouse cTAL is predominantly a passive process, driven by the lumen-positive PDte.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7689239&dopt=Abstract
Am J Physiol. 1987 Aug;253(2 Pt 1):C343-7.
Cl(-)-selective microelectrodes: sensitivity to anionic Cl- transport inhibitors.
Chao AC, Armstrong WM.
Cl(-)-selective microelectrodes, containing Corning code 477315 or 477913 liquid ion exchangers, are often used to measure extra- and intracellular Cl- activities in the presence of Cl- transport inhibitors such as furosemide, bumetanide, and the stilbene sulfonic acid derivative 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). Because these inhibitors are anions in the physiological pH range and have relatively high lipid solubilities, they would be expected to interfere with the response to Cl- of these microelectrodes. Preliminary reports have confirmed this expectation. We examined the effect of furosemide, bumetanide, and SITS on the Cl(-)-selective barrels of double-barreled microelectrodes containing Corning code 477315 liquid anion exchanger and suitable for impaling small cells (e.g., epithelial cells). The results showed that at pH 8.2 in pure solutions of furosemide and bumetanide, these microelectrodes gave linear responses to the logarithm of furosemide or bumetanide concentrations ranging from 1 X 10(-2) to 1 X 10(-4) M. In the physiological pH range both these inhibitors (in concentrations of 0.1 mM) interfered significantly with the response of the microelectrodes to Cl- (in concentrations ranging from 100 to 1 mM). Calculated electrode sensitivities, relative to Cl-, were approximately 150 for both these compounds. Microelectrodes of this type appeared to be approximately 1,000 times as sensitive toward SITS as they were toward Cl-.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3618768&dopt=Abstract
Pharmacol Res Commun. 1984 Mar;16(3):227-41.
Inhibition studies of microsomal UDP-glucuronosyltransferase activities by furosemide and salicylamide.
Boutin JA, Thomassin J, Siest G, Batt AM.
Contrarily to cytochrome P-450, a few inhibitors of UDP-glucuronosyltransferase have been described. We verified the nature of the in vitro inhibition due to furosemide, using 4 different aglycones (morphine, p-nitrophenol, borneol and eugenol) presumably belong may to different clusters of UDP-glucuronosyltransferase activities. The variations of these corresponding kinetic parameters (Km, Vmax, specific activities) must correspond to different inhibition mechanisms of furosemide, for example different site(s) of fixation in the area of the active site of UDPGT. Because these variations were not as classically described, we checked the impact of furosemide pretreatment on in vitro levels of different UDPGT activities. We compared these result, with another inhibitor (salicylamide). The apparent induction due to the both molecules enforced the hypothesis of a complexe inhibition mechanism.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6425870&dopt=Abstract
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