Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00514 (Amiloride)
 1,513 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro effect of various diuretics on rat kidney adenylate cyclase was investigated in crude homogenates of the cortex, the outer and inner medulla. 10-3 M furosemide inhibited adenylate cyclase by 40% in the cortex, by 16% in the outer medulla and by 43% in the inner medulla. 10-3 M ethacrynic acid inhibited adenylate cyclase activity by 65% in the cortex, 59% in the outer medulla and by 57% in the inner medulla. Amiloride produced no significant inhibition of the adenylate cyclase reaction. In the cortex, furosemide partially inhibited adenylate cyclase under basal, fluoride-stimulated and parathyroid hormone-stimulated conditions. Ethacrynic acid produced a strong inhibition of adenylate cyclase activation by F- and parathyroid hormone. In the inner medulla 10-2 M F- and 1 mU antidiuretic hormone reversed the furosemide effect on adenylate cyclase. Ethacrynic acid produced a strong inhibition of adenylate cyclase in the presence of F- and antidiuretic hormone. It is suggested that inhibition of renal adenylate cyclase might be a possible mode of action of certain diuretics.
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PMID:Renal adenylate cyclase-effects of diuretics. 18 72

One of the objectives of this study was to determine whether or not the absence of parathyroid hormone (PTH) modifies quantitatively the acute action of chlorothiazide (CTZ) to lower the clearance ratio, CCa/CNa. The same group of dogs was studied with standard clearance techniques before and after thyroparathyroidectomy (T-PTX), and after T-PTX during the infusion of PTH. There was no significant difference in the response to CTZ before or after T-PTX, or during the infusion of PTH. The effects of PTH and a maximally effective dose of CTZ were additive. A second objective of this work was to ascertain whether or not two other diuretics which act on the distal tubule, amiloride and triamterene, had actions on CCa/CNa similar to that of CTZ. Amiloride caused a reduction in CCa/CNa which, even at maximally effective doses, was much smaller than the effect of CTZ. Maximally effective doses of amiloride and CTZ had additive actions. Triamterene was evaluated at only one dose; it also lowered the ratio CCa/CNa.
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PMID:Relationship between clearances of Ca and Na: effect of distal diuretics and PTH. 125 11

The present study was performed to investigate the regulation of cytosolic pH (pHi) and DNA synthesis by parathyroid hormone(PTH) and PTH-related peptide (PTHrP) in osteoblasts, using osteoblastic osteosarcoma cells, UMR-106 which possessed PTH-responsive dual signal transduction systems (cAMP-dependent protein kinase (PKA) and calcium/protein kinase C [Ca/PKC]) and amiloride-inhibitable Na+/H+ exchange system. Both human (h)PTH-(1-34) and hPTHrP-(1-34) caused a progressive decrease in pHi and the inhibition of [3H]thymidine incorporation (TdR) to the same degree in a dose-dependent manner with a minimal effective dose of 10(-10) M. Dibutyryl cAMP (10(-4) M and Sp-cAMPS (10(-4) M), a direct stimulator of PKA also caused a progressive decrease in pHi, and calcium ionophores (A23187 and ionomycin, 10(-6) M) caused a transient decrease in pHi. Pretreatment with amiloride (0.3 mM) mostly blocked dbcAMP- and Sp-cAMPS-induced decrease in pHi but did not affect calcium ionophore-induced decrease in pHi. In the presence of amiloride, PTH and PTHrP caused a transient decrease in pHi, which was similar to the pattern of calcium ionophore-induced change in pHi. Amiloride did not affect the inhibition of TdR by PTH or PTHrP as well as that by cAMP analogues or calcium ionophores. The present study indicated that PTH and PTHrP caused cytosolic acidification through PKA-inhibited Na+/H+ exchange and increased cytosolic calcium-induced pathway and that the regulation of DNA synthesis by PTH and PTHrP was not via Na+/H+ exchange system.
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PMID:Second messenger signaling in the regulation of cytosolic pH and DNA synthesis by parathyroid hormone (PTH) and PTH-related peptide in osteoblastic osteosarcoma cells: role of Na+/H+ exchange. 132 38

Distal bright convoluted tubules (DCTb) were microdissected from rabbit kidney cortex and cultured in a hormonally defined medium. The quality and the degree of polarization of the growing epithelia were assessed by indirect immunofluorescence studies using a monoclonal antibody raised against the apical membrane of the DCTb in situ. The cultured monolayers had a high hexokinase activity and a low gamma-glutamyl transferase activity compared with cultured proximal convoluted tubules. Adenosine 3',5'-cyclic monophosphate production was stimulated by calcitonin and insensitive to parathyroid hormone, vasopressin, and isoproterenol. Both 20- and 30-day-old cultures developed an apical-negative transepithelial potential of -3.1 and -22.3 mV, respectively. Amiloride reversibly reduced the voltage by 90% only when applied on the apical side of the monolayers. Phenamil (10(-8), 10(-6) M) had the same effect as amiloride. Calcitonin reversibly decreased the transepithelial voltage. These data support the hypothesis that, in the DCTb in primary culture, the transepithelial voltage is due to the presence of Na channels and that calcitonin modulates this transport pathway.
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PMID:Electrical properties of rabbit early distal convoluted tubule in primary culture. 256 36

Na+ transport was evaluated in brush border membrane vesicles isolated from the human placental villous tissue. Na+ uptake was assayed by the rapid filtration technique in the presence and the absence of an uphill pH gradient. Amiloride strongly decreased Na+ uptake whether a pH gradient was present or not. In pH gradient conditions (pH 7.5 in and 9.0 out), 1 mM amiloride decreased the 10 mM Na+ uptake by 84%. In the absence of pH gradient (pH 7.5 in and out), Na+ uptake was lower but still sensitive to amiloride. The Lineweaver-Burk plot of Na+ uptake consistently showed a single kinetics. Increasing the pH gradient decreased Km values of the amiloride-sensitive Na+ uptake, leaving the Vmax unchanged. In the absence of a pH gradient, the amiloride sensitive Na+ transport was maximal at pH 7.5. Here again, a single kinetics was observed, and pH influenced exclusively the Km of Na+. Since ethylisopropylamiloride, the specific Na/H exchanger inhibitor mimicked the effects of amiloride, decreasing by 98% the 10 mM Na+ uptake, whereas benzamil, the Na+ channel blocker, had no effect, it was concluded that the amiloride sensitive Na+ uptake was predominantly or exclusively due to a Na+-H+ exchanger activity. K+ in trans-position significantly decreased the amiloride sensitive uptake. In contrast, the presence of the cation in cis-position had no effect. The amiloride resistant Na+ transport was neither influenced by pH, nor saturable. Incubation of the placental tissue with 100 microM or 1 mM dibutyryl cAMP, 0.1 or 1 microM phorbol myristate acetate, 10(-7) M insulin, 10(-10) M angiotensin II, or 10(-8) M human parathyroid hormone (PTH) did not influence Na+ transport by subsequently prepared brush border membranes. Finally, we failed to demonstrate any Na+-H+ exchange activity in the basal plasma membrane. These results indicate that (1) in the absence of cosubstrates such as phosphate and aminoacids, the Na+-H+ exchange is probably the unique mechanism of Na+ transport by the placental brush border membrane, (2) the placental isoform of the exchanger is not regulated by PTH, angiotensin, nor insulin and, therefore, is different from the isoform present in the renal brush border membrane, and (3) there is no exchanger activity in the basal plasma membrane.
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PMID:Na+ transport by human placental brush border membranes: are there several mechanisms? 869 42