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

Amiloride, a potassium sparing diuretic, is known to interact with a number of ion transport systems, receptors and enzymes. Here, we report on the interaction between this drug and the adenosine A1 receptor as present in calf brain membranes. Adenosine A1 receptors are characterized by a subnanomolar affinity for the antagonists [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and the agonist [3H]N6-R-1-phenyl-2-propyladenosine ([3H]PIA). Amiloride displaces both agonist and antagonist binding with a Ki value in the low micromolar range. This inhibition is counteracted by NaCl and protons, in contrast to the binding of [3H]PIA and [3H]DPCPX. The results suggest that amiloride interacts with the adenosine A1 receptor at a site distinct from the ligand binding site. In order to elucidate the role of one of the ion transport systems known to be inhibited by amiloride, eight amiloride analogues with different sensitivities for these systems were tested. The potency and order of potency of these compounds towards adenosine A1 receptors excludes the involvement of the epithelial Na+ channel, Na+/H+ exchanger or Na+/Ca2+ exchanger.
 ...
PMID:Interaction of amiloride and its analogues with adenosine A1 receptors in calf brain. 214 55

Amiloride analogs that were designed to inhibit three types of Na+ transport systems (the epithelial Na+ channel, the Na+/H+ antiporter, and the Na+/Ca++ exchanger) were applied to the tongue of the gerbil to determine their effects of electrophysiological taste responses to NaCl, CaCl2, sucrose, and glutamic acid. The pattern of responses from the chorda tympani nerve indicates that the taste of NaCl is almost totally accounted for by the epithelial Na+ channel. Phenamil, an amiloride analog which specifically blocks the epithelial Na+ channel at low concentrations, suppressed the taste responses to 0.03 M NaCl by 97%. The pattern of responses also indicates that the Na+/H+ antiporter and the Na+/Ca2+ exchanger do not mediate salt taste in the gerbil. None of the amiloride analogs blocked taste responses to CaCl2, sucrose, or glutamic acid. It is concluded that the salty taste of NaCl in the gerbil is almost totally mediated by the epithelial Na+ channel, and the kinetics of this channel are identical to amiloride-sensitive sodium channels in other systems.
 ...
PMID:The effect of amiloride analogs on taste responses in gerbil. 216 58

Amiloride, an inhibitor of the Na+/Ca2+ exchanger, blocked the hydrolysis of inositol phospholipids in mouse cerebrocortical slices induced by the sodium channel activator veratridine, by KCl, or by the sodium ionophore monensin; there was no inhibition by A 23187, a Ca2+ ionophore, or by serotonin. It is concluded that agents that increase intracellular Na2+ stimulate inositide hydrolysis by an indirect effect via Na+/Ca2+ exchange.
 ...
PMID:Evidence for the involvement of Na+/Ca2+ exchange in the stimulation of inositol phospholipid hydrolysis by sodium channel activation and depolarization. 254 15

Amiloride inhibits most plasma membrane Na+ transport systems. We have reviewed the pharmacology of inhibition of these transporters by amiloride and its analogs. Thorough studies of the Na+ channel, the Na+/H+ exchanger, and the Na+/Ca2+ exchanger, clearly show that appropriate modification of the structure of amiloride will generate analogs with increased affinity and specificity for a particular transport system. Introduction of hydrophobic substituents on the terminal nitrogen of the guanidino moiety enhances activity against the Na+ channel; whereas addition of hydrophobic (or hydrophilic) groups on the 5-amino moiety enhances activity against the Na+/H+ exchanger. Activity against the Na+/Ca2+ exchanger and Ca2+ channel is increased with hydrophobic substituents at either of these sites. Appropriate modification of amiloride has produced analogs that are several hundred-fold more active than amiloride against specific transporters. The availability of radioactive and photoactive amiloride analogs, anti-amiloride antibodies, and analogs coupled to support matrices should prove useful in future studies of amiloride-sensitive transport systems. The use of amiloride and its analogs in the study of ion transport requires a knowledge of the pharmacology of inhibition of transport proteins, as well as effects on enzymes, receptors, and other cellular processes, such as DNA, RNA, and protein synthesis, and cellular metabolism. One must consider whether the effects seen on various cellular processes are direct or due to a cascade of events triggered by an effect on an ion transport system.
 ...
PMID:Amiloride and its analogs as tools in the study of ion transport. 285 54