Modification of potassium-evoked release of noradrenaline by various ions and agents.

1 Release of noradrenaline (NA) from isolated spleen slices of the cat by high K(+) and tetraethylammonium (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 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 [(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 mM EGTA. Release by TEA was blocked in Ca(2+)-free medium containing 5 mM EGTA, and by La(3+) or Mn(2+).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 mM TEA 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 Ca(2+) activated by depolarization.6 Phenoxybenzamine (3.3 muM) 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 C(6), but was markedly attenuated when TEA was applied 10 min after the start of perfusion with high K(+).