Disease relevance of Methylisobutylamiloride

• Increases in Na(i) and [Ca](i) were inhibited by the Na(+)/H(+) exchange inhibitor methylisobutylamiloride (MIA, 40 microM; P < 0.05), as well as by increasing perfusate osmolarity (+30 mosM) immediately before and during hypoxia (P < 0.05) [1].
• Hearts treated with the Na(+)/H(+) exchange inhibitor 5-(N-methyl-N-isobutyl)amiloride (MIA) also showed an enhanced recovery after ischemia (DP 62+/-9%) [2].

High impact information on Methylisobutylamiloride

• In addition, pretreatment with 10 microM of the Na(+)-H+ exchange inhibitor 5-(N-methyl-N-isobutyl)-amiloride significantly attenuated endothelin-induced effects on the intracellular Ca2+ transient and contraction during acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)[3]
• The interaction of 5-(N-methyl-N-isobutyl)amiloride (MIBA) with brush-border membrane vesicles isolated from normal human term placentas was investigated using two parameters: binding and transport [4].
• Specific interaction of 5-(N-methyl-N-isobutyl)amiloride with the organic cation-proton antiporter in human placental brush-border membrane vesicles. Transport and binding [4].
• In medium lacking sodium bicarbonate the intracellular alkalinization via the CD2 structure could be blocked by the amiloride analogue 5-(N-methyl-N-isobutyl)amiloride (MIA), which indicates that this increase in pH is mediated by the amiloride-sensitive Na+/H+ antiporter [5].
• Kinetic studies revealed that 5-(N-methyl-N-isobutyl)amiloride (MIA) was a more potent inhibitor of the antiport than amiloride (cf. apparent Ki of 174 nM and 6 microM, respectively) [6].

Biological context of Methylisobutylamiloride

• Allosteric regulation of [3H]spiperone binding by methylisobutylamiloride could also be observed in saturation and inhibition binding experiments [7].
• 5. An amiloride analogue, 5-(N-methyl-N-isobutyl)amiloride (MIBA), inhibited only the sustained PIE with an IC50 of 0.3 microM which is approximately two orders of magnitude lower than amiloride [8].
• Perfusion with a Ca2+-free solution induced shrinkage of the AT-II cell volume in the absence or presence of amiloride (1 microm, an inhibitor of Na+ channels); however, it did not in the presence of 5-(N-methyl-N-isobutyl)-amiloride (MIA, an inhibitor of Na+-H+ exchange) [9].

Anatomical context of Methylisobutylamiloride

• Increases in [Ca2+]i were significantly (P < 0.005) attenuated by the Na+/H+ exchange blocker 5-(N-methyl-N-isobutyl)-amiloride in neurons and astrocytes [10].
• In human gut epithelial cells, NHE inhibition using a variety of agents, including amiloride, 5-(N-methyl-N-isobutyl)amiloride, 5-(N-ethyl-N-isopropyl)- amiloride, harmaline, clonidine, and cimetidine, suppressed interleukin-8 (IL-8) production [11].
• Extracellular ATP stimulated 86Rb efflux from lymphocytes 10-fold and this increment was inhibited by the amiloride analogs in a rank order of potency 5-(N-methyl-N-isobutyl)amiloride greater than 5-(N,N-hexamethylene)amiloride greater than 5-(N-ethyl-N-isopropyl)amiloride greater than amiloride [12].
• As a means to characterize the Na(+)-H+ exchanger in the bovine corneal epithelium, we determined the binding properties of [3H] methylisobutylamiloride (MIA) to a fraction enriched in plasma membrane from this tissue [13].
• The coadministration of either amiloride, benzamil, 5-(N, N-dimethyl)-amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, or 5-(N-methyl-N-isobutyl)-amiloride all dose responsively increased the frequency and severity of forelimb malformations compared to acetazolamide alone [14].

Associations of Methylisobutylamiloride with other chemical compounds

• Exposure to lactate at reduced extracellular pH (pHo = 6.4) produced a larger rise in [Na+]i. In the presence of the Na/H exchange inhibitor 5-(N-methyl-N-isobutyl)-amiloride exposure to lactate caused a small fall in [Na+]i at pHo 7.4 and 6 [15].
• These discharges were suppressed by the GABAB receptor agonist baclofen (10 microM), and were prevented by amiloride and its analogs 5-(N,N-dimethyl)-amiloride, 5-(N-methyl-N-isobutyl)-amiloride and benzamil, but not by triamterene (100-500 microM) [16].
• The effects of amiloride and its analogues (3',4'-dichlorobenzamil (DCB), 2',4'-dimethylbenzamil (DMB), 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and 5-(N-methyl-N-isobutyl)amiloride (MIBA)) on cardiac ion transporters (Na+/Ca2+ exchanger, Na+/H+ exchanger, Na+ pump and Ca2+ pump) and their cytotoxicities were tested in cardiac myocytes [17].

Gene context of Methylisobutylamiloride

• In contrast to zinc, methylisobutylamiloride (MIA) binding to the wild-type D4 receptor was virtually unaffected by sodium [18].
• The ECAR responses to SS were modestly attenuated by methylisobutylamiloride (MIA), an inhibitor of the ubiquitous Na(+)-H+ exchanger NHE1 [19].
• The responses mediated by all three alpha(2)-adrenoceptor subtypes were partly inhibited by the sodium-hydrogen (Na(+)/H(+)) exchange inhibitor, MIA (5-(N-methyl-N-isobutyl)-amiloride) [20].

References