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Modification of potassium‐evoked release of noradrenaline by various ions and agents
Author(s) -
Kirpekar S.M.,
Prat J.C.,
Schiavone M.T.
Publication year - 1983
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1983.tb09392.x
Subject(s) - egta , chemistry , potassium , tetrodotoxin , hexamethonium , incubation , 4 aminopyridine , long term potentiation , biophysics , calcium , nuclear chemistry , potassium channel , biochemistry , biology , receptor , organic chemistry
1 Release of noradrenaline (NA) from isolated spleen slices of the cat by high K + and tetra‐ethylammonium (TEA) was investigated. Studies were conducted with spleen slices whose tissue stores were prelabelled with [ 3 H]‐noradrenaline ([ 3 H]‐NA). 2 Release by high K + was related to the K + concentration of the incubation medium. Release of [ 3 H]‐NA by 28.5 m m K + was only barely detectable over the background, while 70 m m K + enhanced release to more than 600% of the background output. Tetrodotoxin (TTX) did not block responses to 28.5 or 35 m m K + . 3 Background release was not modified by 1 or 3 m m TEA, but 10 and 30 m m TEA enhanced the release of [ 3 H]‐NA by about 50% and 150%, respectively, over the background level. Neither TTX nor hexamethonium (C 6 ) blocked the TEA response. Release by TEA was also not blocked in Ca 2+ ‐free medium or in Ca 2+ ‐free medium containing up to 3 m m EGTA. Release by TEA was blocked in Ca 2+ ‐free medium containing 5 m m EGTA, and by La 3+ or Mn 2+ . 4 The response to 35 m m K + was not modified by 1 or 3 m m TEA; 10 m m TEA had an additive effect; and 30 m m TEA with 35 m m K + produced a response which was greater than the simple sum of responses to 35 m m K + and 30 m m TEA. At 45 m m K + , 3 and 10 m m TEA potentiated the response, and at 30 m m K + only 1 m m TEA showed potentiation. TTX did not alter the response to high K + plus TEA. 5 When TEA (30 m m ) was added during prolonged incubation with 140 m m K + , the response was only slightly enhanced. This suggests that a large part of the secretory response to TEA is mediated through mobilization of Ca 2+ activated by depolarization. 6 Phenoxybenzamine (3.3 μ m ) potentiated responses to 35 and 140 m m K + by about 50%, and TTX did not influence this potentiation. Acetylcholine (ACh) blocked responses to 28.5 and 35 m m K + , and 1 m m TEA antagonized this ACh blockade. 7 In the perfused adrenal gland of the cat, the secretory response to TEA was related to its concentration. The response was not diminished by low Na + , TTX, or C 6 , but was markedly attenuated when TEA was applied 10 min after the start of perfusion with high K + .