Spontaneous [3H]noradrenaline release from the main pulmonary artery of the rabbit induced by sodium-pump inhibition

T. L. Torok, Z. Salamon, T. T. Nguyen, K. Magyar

Research output: Contribution to journalArticle

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Abstract

Inhibition of Na pump either by ouabain (10-4) or by K removal increased the [3H]noradrenaline ([3H]NA release from the isolated main pulmonary artery of the rabbit in the presence of neuronal (cocaine, 3 x 10-5 M) and extraneuronal (corticosterone, 5 x 10-5 M) uptake blockers. The ouabain-evoked [3H]NA release began after a delay of about 30 min and peaked after 66 min of ouabain application. Both times were shortened by omission of K from the external medium. About 90% of ouabain-evoked [3H]NA release proved to be external Ca concentration ([Ca]0) dependent and the peak effect was delayed by about 80 min in Ca-free (+ 1 mM EGTA) solution. In the presence of external Ca (2.5 mM) the [3H]NA-releasing effect of 'K-free' treatment was much less pronounced than that of 10-4 M ouabain, the initial delay in transmitter release was shorter (10-15 min) and the peak effect developed earlier (at 42 min). On readmission of K the [3H]NA release recovered quickly to the original value. Ca removal did not antagonize the transmitter release observed in K-free solution, but the peak release was delayed by about 90 min. A low concentration of ouabain (10-5 M) failed to produce transmitter release in the presence of normal external K, but markedly increased the release in K-free solution. The release was much bigger than the sum of their separate effects, and the rate of rise was faster than when 10-4 M ouabain was applied in normal solution. Excess Ca (7.5; 15 mM) inhibited the [3H]NA release observed in K-free solution. 7.5 mM-Ca also delayed the transmitter-releasing action of 10-4 M ouabain, an effect antagonized by omission of K from the external medium. The mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP, 10-5 M) significantly increased the [3H]NA release in Ca-free, 1 mM EGTA-containing solution, and enhanced the effects of ouabain (10-4 M). The Ca ionophore A23187 (10-5 M) also significantly increased the [3H]NA release in the absence of external Ca and in the presence of 1 mM EGTA. Again, in the presence of A23187 the effects of 10-4 M ouabain in releasing neurotransmitter were enhanced. When CCCP and A23187 were applied together in Ca-free, EGTA solution the [3H]NA releasing action of ouabain was still apparent. Veratridine (10-4 M) enhanced the transmitter release in the absence of external Ca in a tetrodotoxin (TTX)-sensitive manner. After veratridine treatment the action of ouabain was totally abolished. However, in the presence of TTX (10-7 and 3 x 10-7 M) which by itself significantly inhibited the veratridine-evoked transmitter release the action of ouabain persisted. It is suggested that excess Ca, like external K, inhibits the transmitter-releasing effect of Na-pump inhibition, furthermore that in the absence of external Ca the ouabain-evoked transmitter release is the result of Ca release from internal stores rather than Na-pump inhibition per se.

Original languageEnglish
Pages (from-to)841-865
Number of pages25
JournalQuarterly Journal of Experimental Physiology
Volume69
Issue number4
Publication statusPublished - 1984

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Sodium-Potassium-Exchanging ATPase
Ouabain
Pulmonary Artery
Norepinephrine
Rabbits
Egtazic Acid
Veratridine
Calcimycin
Carbonyl Cyanide m-Chlorophenyl Hydrazone
Tetrodotoxin
Ionophores
Corticosterone
Cocaine

ASJC Scopus subject areas

  • Physiology

Cite this

Spontaneous [3H]noradrenaline release from the main pulmonary artery of the rabbit induced by sodium-pump inhibition. / Torok, T. L.; Salamon, Z.; Nguyen, T. T.; Magyar, K.

In: Quarterly Journal of Experimental Physiology, Vol. 69, No. 4, 1984, p. 841-865.

Research output: Contribution to journalArticle

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abstract = "Inhibition of Na pump either by ouabain (10-4) or by K removal increased the [3H]noradrenaline ([3H]NA release from the isolated main pulmonary artery of the rabbit in the presence of neuronal (cocaine, 3 x 10-5 M) and extraneuronal (corticosterone, 5 x 10-5 M) uptake blockers. The ouabain-evoked [3H]NA release began after a delay of about 30 min and peaked after 66 min of ouabain application. Both times were shortened by omission of K from the external medium. About 90{\%} of ouabain-evoked [3H]NA release proved to be external Ca concentration ([Ca]0) dependent and the peak effect was delayed by about 80 min in Ca-free (+ 1 mM EGTA) solution. In the presence of external Ca (2.5 mM) the [3H]NA-releasing effect of 'K-free' treatment was much less pronounced than that of 10-4 M ouabain, the initial delay in transmitter release was shorter (10-15 min) and the peak effect developed earlier (at 42 min). On readmission of K the [3H]NA release recovered quickly to the original value. Ca removal did not antagonize the transmitter release observed in K-free solution, but the peak release was delayed by about 90 min. A low concentration of ouabain (10-5 M) failed to produce transmitter release in the presence of normal external K, but markedly increased the release in K-free solution. The release was much bigger than the sum of their separate effects, and the rate of rise was faster than when 10-4 M ouabain was applied in normal solution. Excess Ca (7.5; 15 mM) inhibited the [3H]NA release observed in K-free solution. 7.5 mM-Ca also delayed the transmitter-releasing action of 10-4 M ouabain, an effect antagonized by omission of K from the external medium. The mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP, 10-5 M) significantly increased the [3H]NA release in Ca-free, 1 mM EGTA-containing solution, and enhanced the effects of ouabain (10-4 M). The Ca ionophore A23187 (10-5 M) also significantly increased the [3H]NA release in the absence of external Ca and in the presence of 1 mM EGTA. Again, in the presence of A23187 the effects of 10-4 M ouabain in releasing neurotransmitter were enhanced. When CCCP and A23187 were applied together in Ca-free, EGTA solution the [3H]NA releasing action of ouabain was still apparent. Veratridine (10-4 M) enhanced the transmitter release in the absence of external Ca in a tetrodotoxin (TTX)-sensitive manner. After veratridine treatment the action of ouabain was totally abolished. However, in the presence of TTX (10-7 and 3 x 10-7 M) which by itself significantly inhibited the veratridine-evoked transmitter release the action of ouabain persisted. It is suggested that excess Ca, like external K, inhibits the transmitter-releasing effect of Na-pump inhibition, furthermore that in the absence of external Ca the ouabain-evoked transmitter release is the result of Ca release from internal stores rather than Na-pump inhibition per se.",
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T1 - Spontaneous [3H]noradrenaline release from the main pulmonary artery of the rabbit induced by sodium-pump inhibition

AU - Torok, T. L.

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AU - Nguyen, T. T.

AU - Magyar, K.

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N2 - Inhibition of Na pump either by ouabain (10-4) or by K removal increased the [3H]noradrenaline ([3H]NA release from the isolated main pulmonary artery of the rabbit in the presence of neuronal (cocaine, 3 x 10-5 M) and extraneuronal (corticosterone, 5 x 10-5 M) uptake blockers. The ouabain-evoked [3H]NA release began after a delay of about 30 min and peaked after 66 min of ouabain application. Both times were shortened by omission of K from the external medium. About 90% of ouabain-evoked [3H]NA release proved to be external Ca concentration ([Ca]0) dependent and the peak effect was delayed by about 80 min in Ca-free (+ 1 mM EGTA) solution. In the presence of external Ca (2.5 mM) the [3H]NA-releasing effect of 'K-free' treatment was much less pronounced than that of 10-4 M ouabain, the initial delay in transmitter release was shorter (10-15 min) and the peak effect developed earlier (at 42 min). On readmission of K the [3H]NA release recovered quickly to the original value. Ca removal did not antagonize the transmitter release observed in K-free solution, but the peak release was delayed by about 90 min. A low concentration of ouabain (10-5 M) failed to produce transmitter release in the presence of normal external K, but markedly increased the release in K-free solution. The release was much bigger than the sum of their separate effects, and the rate of rise was faster than when 10-4 M ouabain was applied in normal solution. Excess Ca (7.5; 15 mM) inhibited the [3H]NA release observed in K-free solution. 7.5 mM-Ca also delayed the transmitter-releasing action of 10-4 M ouabain, an effect antagonized by omission of K from the external medium. The mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP, 10-5 M) significantly increased the [3H]NA release in Ca-free, 1 mM EGTA-containing solution, and enhanced the effects of ouabain (10-4 M). The Ca ionophore A23187 (10-5 M) also significantly increased the [3H]NA release in the absence of external Ca and in the presence of 1 mM EGTA. Again, in the presence of A23187 the effects of 10-4 M ouabain in releasing neurotransmitter were enhanced. When CCCP and A23187 were applied together in Ca-free, EGTA solution the [3H]NA releasing action of ouabain was still apparent. Veratridine (10-4 M) enhanced the transmitter release in the absence of external Ca in a tetrodotoxin (TTX)-sensitive manner. After veratridine treatment the action of ouabain was totally abolished. However, in the presence of TTX (10-7 and 3 x 10-7 M) which by itself significantly inhibited the veratridine-evoked transmitter release the action of ouabain persisted. It is suggested that excess Ca, like external K, inhibits the transmitter-releasing effect of Na-pump inhibition, furthermore that in the absence of external Ca the ouabain-evoked transmitter release is the result of Ca release from internal stores rather than Na-pump inhibition per se.

AB - Inhibition of Na pump either by ouabain (10-4) or by K removal increased the [3H]noradrenaline ([3H]NA release from the isolated main pulmonary artery of the rabbit in the presence of neuronal (cocaine, 3 x 10-5 M) and extraneuronal (corticosterone, 5 x 10-5 M) uptake blockers. The ouabain-evoked [3H]NA release began after a delay of about 30 min and peaked after 66 min of ouabain application. Both times were shortened by omission of K from the external medium. About 90% of ouabain-evoked [3H]NA release proved to be external Ca concentration ([Ca]0) dependent and the peak effect was delayed by about 80 min in Ca-free (+ 1 mM EGTA) solution. In the presence of external Ca (2.5 mM) the [3H]NA-releasing effect of 'K-free' treatment was much less pronounced than that of 10-4 M ouabain, the initial delay in transmitter release was shorter (10-15 min) and the peak effect developed earlier (at 42 min). On readmission of K the [3H]NA release recovered quickly to the original value. Ca removal did not antagonize the transmitter release observed in K-free solution, but the peak release was delayed by about 90 min. A low concentration of ouabain (10-5 M) failed to produce transmitter release in the presence of normal external K, but markedly increased the release in K-free solution. The release was much bigger than the sum of their separate effects, and the rate of rise was faster than when 10-4 M ouabain was applied in normal solution. Excess Ca (7.5; 15 mM) inhibited the [3H]NA release observed in K-free solution. 7.5 mM-Ca also delayed the transmitter-releasing action of 10-4 M ouabain, an effect antagonized by omission of K from the external medium. The mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP, 10-5 M) significantly increased the [3H]NA release in Ca-free, 1 mM EGTA-containing solution, and enhanced the effects of ouabain (10-4 M). The Ca ionophore A23187 (10-5 M) also significantly increased the [3H]NA release in the absence of external Ca and in the presence of 1 mM EGTA. Again, in the presence of A23187 the effects of 10-4 M ouabain in releasing neurotransmitter were enhanced. When CCCP and A23187 were applied together in Ca-free, EGTA solution the [3H]NA releasing action of ouabain was still apparent. Veratridine (10-4 M) enhanced the transmitter release in the absence of external Ca in a tetrodotoxin (TTX)-sensitive manner. After veratridine treatment the action of ouabain was totally abolished. However, in the presence of TTX (10-7 and 3 x 10-7 M) which by itself significantly inhibited the veratridine-evoked transmitter release the action of ouabain persisted. It is suggested that excess Ca, like external K, inhibits the transmitter-releasing effect of Na-pump inhibition, furthermore that in the absence of external Ca the ouabain-evoked transmitter release is the result of Ca release from internal stores rather than Na-pump inhibition per se.

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