Effects of amiloride and its analogues on [3H]batrachotoxinin-A 20-α benzoate binding, [3H]tetracaine binding and 22Na influx

Velly, J; Grima, Michèle; Decker, Nicole; Cragoe, Edward J.; Schwartz, Jean

doi:10.1016/0014-2999(88)90047-7

Cited by 22 publications

(13 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we have shown that EIPA and MIBA also inhibit the Na+/Ca2+ exchanger and the Ca 21 pump with the same potency (IC50 values: 70-90 pM) as that for the Na+/H+ exchanger in membrane preparations. EIPA has been reported to inhibit the voltage-dependent Na+ channel of rat brain synaptosomes with an IC50 value of 6.1 pM (18). These findings suggest that EIPA and MIBA are not specific inhibitors of the Na+ /H+ exchanger; therefore, even if Na influx into cells is inhibited by EIPA or MIBA, we can not conclude that this is solely due to the involvement of the Na+/H+ exchanger, at least in membrane preparations.…”

Section: Measurement Of Membrane Ion Transporter Activitiescontrasting

confidence: 41%

Non-selective Effects of Amiloride and Its Analogues on Ion Transport Systems and Their Cytotoxicities in Cardiac Myocytes

Murata¹,

Harada²,

Nakajima³

et al. 1995

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-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 Ca 21 pump) and their cytotoxicities were tested in cardiac myocytes. All the tested compounds showed concentration-dependent inhibitory effects on the ion transporters studied in canine cardiac sarcolemmal vesicles. The concentrations (NM) of amiloride, DCB, DMB, EIPA and MIBA required to produce 50% inhibition were > 1000, 19, 10, 83 and 84, respectively, for the Na+/Ca2+ exchanger; 130, 73, 63, 16 and 14 for the Na+/H+ exchanger; > 1000, 72, > 300, > 300 and > 300 for the Na+ pump; and > 1000, 37, 93, 90 and 70 for the Ca 21 pump, respectively. Furthermore, these agents induced cell death in isolated rat cardiac myocytes and the 50% lethal concentrations (,uM) were > 1000, 9.2, 30, 16 and 17, respectively. These findings demonstrate that amiloride and its analogues have non-selective inhibitory effects on cardiac ion transporters and cytotoxicity in cardiomyocytes. When these drugs are employed as experimental tools to investigate the involvement of ion transporters in cell functions, the results must be interpreted with caution.

show abstract

Section: Measurement Of Membrane Ion Transporter Activitiescontrasting

confidence: 41%

Non-selective Effects of Amiloride and Its Analogues on Ion Transport Systems and Their Cytotoxicities in Cardiac Myocytes

Murata¹,

Harada²,

Nakajima³

et al. 1995

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…Amiloride and harmaline both have nonspecific effects that include partial blockade of Na channels (Velly et al, 1988;Deecher et al, 1992). Both amiloride and harmaline slightly decreased CAP amplitudes before the onset of anoxia (Fig.…”

Section: Amiloride and Harmalinementioning

confidence: 94%

Anoxie Injury in the Rat Spinal Cord: Pharmacological Evidence for Multiple Steps in Ca²⁺-Dependent Injury of the Dorsal Columns

Imaizumi¹,

Kocsis²,

Waxman³

1997

Journal of Neurotrauma

View full text Add to dashboard Cite

To examine anoxic injury in spinal cord white matter, we studied axonal conduction in the dorsal columns during and following a standard 60 min anoxic insult at 36 degrees C. Perfusion of the spinal cord in 0-Ca2+ Ringer solution resulted in significantly improved recovery of the compound action potential. Similarly, removal of Na+ from the perfusate resulted in significantly improved recovery of conduction in dorsal column axons. Exposure of the anoxic spinal cord to the Na+ channel blocker tetrodotoxin (TTX), the Na-Ca exchange blockers benzamil and bepridil, Na(+)-H+ exchange blockers amiloride and harmaline, and perfusion in Ringer solution with pH adjusted to 6.4, all resulted in improved recovery. The tertiary anesthetics procaine and lidocaine, as well as phenytoin and carbamazepine, also resulted in improved recovery of compound action potential amplitude after 60 min of anoxia. These results demonstrate that a significant component of irreversible loss of conduction, following anoxic injury of the dorsal columns, is Ca(2+)-dependent. Moreover, these results demonstrate that TTX-inhibitable Na+ channels participate in the pathophysiology of anoxic injury in spinal cord white matter, and indicate that reverse Na-Ca exchange provides a route for at least part of the damaging influx of Ca2+ into an intracellular compartment in anoxic spinal cord white matter. Our results also suggest that extracellular acidosis may have a protective effect on anoxic spinal cord white matter, and support the hypothesis that anoxic injury of spinal cord white matter may involve the Na(+)-H+ exchanger.

show abstract

“…A voltage-gated Na+-selective ion channel is present in electrically excitable cells and is inhibited specifically by the toxins tetrodotoxin and saxitoxin in the nanomolar range. It has recently been shown that amiloride inhibits this channel in both synaptosomes and heart membrane vesicles, as measured by inhibition of veratridine-activated 22Na+ flux across membrane vesicles [80]. b. Voltage-Gated Ca 2+ Channel.…”

Section: F Other Ion Transportersmentioning

confidence: 99%

Amiloride and its analogs as tools in the study of ion transport

1988

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Effects of amiloride and its analogues on [3H]batrachotoxinin-A 20-α benzoate binding, [3H]tetracaine binding and 22Na influx

Cited by 22 publications

References 17 publications

Non-selective Effects of Amiloride and Its Analogues on Ion Transport Systems and Their Cytotoxicities in Cardiac Myocytes

Non-selective Effects of Amiloride and Its Analogues on Ion Transport Systems and Their Cytotoxicities in Cardiac Myocytes

Anoxie Injury in the Rat Spinal Cord: Pharmacological Evidence for Multiple Steps in Ca²⁺-Dependent Injury of the Dorsal Columns

Amiloride and its analogs as tools in the study of ion transport

Contact Info

Product

Resources

About

Effects of amiloride and its analogues on [3H]batrachotoxinin-A 20-α benzoate binding, [3H]tetracaine binding and 22Na influx

Cited by 22 publications

References 17 publications

Non-selective Effects of Amiloride and Its Analogues on Ion Transport Systems and Their Cytotoxicities in Cardiac Myocytes

Non-selective Effects of Amiloride and Its Analogues on Ion Transport Systems and Their Cytotoxicities in Cardiac Myocytes

Anoxie Injury in the Rat Spinal Cord: Pharmacological Evidence for Multiple Steps in Ca2+-Dependent Injury of the Dorsal Columns

Amiloride and its analogs as tools in the study of ion transport

Contact Info

Product

Resources

About

Anoxie Injury in the Rat Spinal Cord: Pharmacological Evidence for Multiple Steps in Ca²⁺-Dependent Injury of the Dorsal Columns