Modification of potassium‐evoked release of noradrenaline by various ions and agents

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Abstract
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 [3H]-noradrenaline ([3H]-NA). 2 Release by high K+ was related to the K+ concentration of the incubation medium. Release of [3H]-NA by 28.5 mm K+ was only barely detectable over the background, while 70 mm K+ enhanced release to more than 600% of the background output. Tetrodotoxin (TTX) did not block responses to 28.5 or 35 mm K+. 3 Background release was not modified by 1 or 3 mm TEA, but 10 and 30 mm TEA enhanced the release of [3H]-NA by about 50% and 150%, respectively, over the background level. Neither TTX nor hexamethonium (C6) blocked the TEA response. Release by TEA was also not blocked in Ca2+-free medium or in Ca2+-free medium containing up to 3 mm EGTA. Release by TEA was blocked in Ca2+-free medium containing 5 mm EGTA, and by La3+ or Mn2+. 4 The response to 35 mm K+ was not modified by 1 or 3 mm TEA; 10 mm TEA had an additive effect; and 30 mm TEA with 35 mm K+ produced a response which was greater than the simple sum of responses to 35 mm K+ and 30 mm TEA. At 45 mm K+, 3 and 10 mmTEA potentiated the response, and at 30 mm K+ only 1 mm TEA showed potentiation. TTX did not alter the response to high K+plus TEA. 5 When TEA (30 mm) was added during prolonged incubation with 140 mm K+, the response was only slightly enhanced. This suggests that a large part of the secretory response to TEA is mediated through mobilization of Ca2+ activated by depolarization. 6 Phenoxybenzamine (3.3 μm) potentiated responses to 35 and 140 mm K+ by about 50%, and TTX did not influence this potentiation. Acetylcholine (ACh) blocked responses to 28.5 and 35 mm K+, and 1 mm 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 C6, but was markedly attenuated when TEA was applied 10 min after the start of perfusion with high K+.

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