Mechanism of norepinephrine release elicited by Na+-K+ adenosine triphosphatase inhibition in the isolated rat kidney

Involvement of voltage-dependent C++ channels

M. M. Mohy El-Din, Kafait Malik

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3 Citations (Scopus)

Abstract

The mechanism by which ouabain and Na+ depletion enhance the release of norepinephrine (NE) was investigated in the isolated rat kidney prelabeled with [3H]NE by examining the efflux of tritium elicited by these stimuli during 1) Ca++ depletion and 2) administration of tetrodotoxin, amiloride and Ca++ channel blockers. In kidneys perfused with Tyrode's solution containing low K+ solution (0.54 mM), ouabain (10-4 M) enhanced tritium efflux markedly by about 20-fold at 30 min. Depletion of Na+ from the perfusion medium also produced an increase in tritium overflow which peaked at 20 min. Administration of tetrodotoxin (0.3 μM) inhibited the effect of ouabain, but not that of Na+ depletion, to increase tritium efflux and perfusion pressure. In contrast, amiloride (180 μM) enhanced the overflow of tritium elicited by ouabain but failed to alter that elicited by Na+ depletion. The rise in perfusion pressure caused by both stimuli was attenuated by amiloride. Omission of Ca++ (1.8 mM) from the perfusion medium inhibited the increase in tritium efflux and perfusion pressure elicited by ouabain and Na+ depletion by 80 and 65%, respectively. The Ca++ channel blockers ω-conotoxin (50 nM), diltiazem (60 μM) and flunarizine (2 μM), but not nifedipine (1.4 μM), inhibited tritium overflow elicited by ouabain. However, nifedipine, diltiazem and flunarizine, but not ω-conotoxin attenuated the tritium overflow elicited by Na+ depletion. The rise in perfusion pressure elicited by ouabain in low K+ and Na+ depletion was inhibited by these Ca++ channel blockers. These data suggest that ouabain in the presence of low K+ promotes the release of adrenergic transmitter by enhancing the influx of Ca++. Ca++ entry may occur through specific Ca++ channels, probably of the N-type, thereby involving a release mechanism similar to that utilized by renal nerve stimulation. However, Na+ depletion promotes release of NE by enhancing influx of Ca++ through a distinct type of Ca++ channel.

Original languageEnglish (US)
Pages (from-to)436-443
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume245
Issue number2
StatePublished - 1988

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Tritium
Ouabain
Adenosine Triphosphatases
Norepinephrine
Kidney
Perfusion
Amiloride
Conotoxins
Flunarizine
Pressure
Diltiazem
Tetrodotoxin
Nifedipine
Adrenergic Agents

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Mechanism of norepinephrine release elicited by Na+-K+ adenosine triphosphatase inhibition in the isolated rat kidney: Involvement of voltage-dependent C++ channels",
abstract = "The mechanism by which ouabain and Na+ depletion enhance the release of norepinephrine (NE) was investigated in the isolated rat kidney prelabeled with [3H]NE by examining the efflux of tritium elicited by these stimuli during 1) Ca++ depletion and 2) administration of tetrodotoxin, amiloride and Ca++ channel blockers. In kidneys perfused with Tyrode's solution containing low K+ solution (0.54 mM), ouabain (10-4 M) enhanced tritium efflux markedly by about 20-fold at 30 min. Depletion of Na+ from the perfusion medium also produced an increase in tritium overflow which peaked at 20 min. Administration of tetrodotoxin (0.3 μM) inhibited the effect of ouabain, but not that of Na+ depletion, to increase tritium efflux and perfusion pressure. In contrast, amiloride (180 μM) enhanced the overflow of tritium elicited by ouabain but failed to alter that elicited by Na+ depletion. The rise in perfusion pressure caused by both stimuli was attenuated by amiloride. Omission of Ca++ (1.8 mM) from the perfusion medium inhibited the increase in tritium efflux and perfusion pressure elicited by ouabain and Na+ depletion by 80 and 65{\%}, respectively. The Ca++ channel blockers ω-conotoxin (50 nM), diltiazem (60 μM) and flunarizine (2 μM), but not nifedipine (1.4 μM), inhibited tritium overflow elicited by ouabain. However, nifedipine, diltiazem and flunarizine, but not ω-conotoxin attenuated the tritium overflow elicited by Na+ depletion. The rise in perfusion pressure elicited by ouabain in low K+ and Na+ depletion was inhibited by these Ca++ channel blockers. These data suggest that ouabain in the presence of low K+ promotes the release of adrenergic transmitter by enhancing the influx of Ca++. Ca++ entry may occur through specific Ca++ channels, probably of the N-type, thereby involving a release mechanism similar to that utilized by renal nerve stimulation. However, Na+ depletion promotes release of NE by enhancing influx of Ca++ through a distinct type of Ca++ channel.",
author = "{Mohy El-Din}, {M. M.} and Kafait Malik",
year = "1988",
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volume = "245",
pages = "436--443",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
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T1 - Mechanism of norepinephrine release elicited by Na+-K+ adenosine triphosphatase inhibition in the isolated rat kidney

T2 - Involvement of voltage-dependent C++ channels

AU - Mohy El-Din, M. M.

AU - Malik, Kafait

PY - 1988

Y1 - 1988

N2 - The mechanism by which ouabain and Na+ depletion enhance the release of norepinephrine (NE) was investigated in the isolated rat kidney prelabeled with [3H]NE by examining the efflux of tritium elicited by these stimuli during 1) Ca++ depletion and 2) administration of tetrodotoxin, amiloride and Ca++ channel blockers. In kidneys perfused with Tyrode's solution containing low K+ solution (0.54 mM), ouabain (10-4 M) enhanced tritium efflux markedly by about 20-fold at 30 min. Depletion of Na+ from the perfusion medium also produced an increase in tritium overflow which peaked at 20 min. Administration of tetrodotoxin (0.3 μM) inhibited the effect of ouabain, but not that of Na+ depletion, to increase tritium efflux and perfusion pressure. In contrast, amiloride (180 μM) enhanced the overflow of tritium elicited by ouabain but failed to alter that elicited by Na+ depletion. The rise in perfusion pressure caused by both stimuli was attenuated by amiloride. Omission of Ca++ (1.8 mM) from the perfusion medium inhibited the increase in tritium efflux and perfusion pressure elicited by ouabain and Na+ depletion by 80 and 65%, respectively. The Ca++ channel blockers ω-conotoxin (50 nM), diltiazem (60 μM) and flunarizine (2 μM), but not nifedipine (1.4 μM), inhibited tritium overflow elicited by ouabain. However, nifedipine, diltiazem and flunarizine, but not ω-conotoxin attenuated the tritium overflow elicited by Na+ depletion. The rise in perfusion pressure elicited by ouabain in low K+ and Na+ depletion was inhibited by these Ca++ channel blockers. These data suggest that ouabain in the presence of low K+ promotes the release of adrenergic transmitter by enhancing the influx of Ca++. Ca++ entry may occur through specific Ca++ channels, probably of the N-type, thereby involving a release mechanism similar to that utilized by renal nerve stimulation. However, Na+ depletion promotes release of NE by enhancing influx of Ca++ through a distinct type of Ca++ channel.

AB - The mechanism by which ouabain and Na+ depletion enhance the release of norepinephrine (NE) was investigated in the isolated rat kidney prelabeled with [3H]NE by examining the efflux of tritium elicited by these stimuli during 1) Ca++ depletion and 2) administration of tetrodotoxin, amiloride and Ca++ channel blockers. In kidneys perfused with Tyrode's solution containing low K+ solution (0.54 mM), ouabain (10-4 M) enhanced tritium efflux markedly by about 20-fold at 30 min. Depletion of Na+ from the perfusion medium also produced an increase in tritium overflow which peaked at 20 min. Administration of tetrodotoxin (0.3 μM) inhibited the effect of ouabain, but not that of Na+ depletion, to increase tritium efflux and perfusion pressure. In contrast, amiloride (180 μM) enhanced the overflow of tritium elicited by ouabain but failed to alter that elicited by Na+ depletion. The rise in perfusion pressure caused by both stimuli was attenuated by amiloride. Omission of Ca++ (1.8 mM) from the perfusion medium inhibited the increase in tritium efflux and perfusion pressure elicited by ouabain and Na+ depletion by 80 and 65%, respectively. The Ca++ channel blockers ω-conotoxin (50 nM), diltiazem (60 μM) and flunarizine (2 μM), but not nifedipine (1.4 μM), inhibited tritium overflow elicited by ouabain. However, nifedipine, diltiazem and flunarizine, but not ω-conotoxin attenuated the tritium overflow elicited by Na+ depletion. The rise in perfusion pressure elicited by ouabain in low K+ and Na+ depletion was inhibited by these Ca++ channel blockers. These data suggest that ouabain in the presence of low K+ promotes the release of adrenergic transmitter by enhancing the influx of Ca++. Ca++ entry may occur through specific Ca++ channels, probably of the N-type, thereby involving a release mechanism similar to that utilized by renal nerve stimulation. However, Na+ depletion promotes release of NE by enhancing influx of Ca++ through a distinct type of Ca++ channel.

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