Chideckel E W, Fedan J S, Mike P
Br J Pharmacol. 1986 Sep;89(1):27-33. doi: 10.1111/j.1476-5381.1986.tb11117.x.
We have previously observed a paradoxical relaxant effect of K+ on guinea-pig isolated trachealis after exposure to polyamines. The purpose of the present study was to evaluate whether the relaxation involved a reduction in the entry of extracellular Ca2+. We therefore investigated the effect of K+ in the presence of Ca2+-entry blocking drugs and in the presence of Ca2+-free solution. In the presence of nifedipine (10(-5) M), verapamil (10(-5) M) or diltiazem (10(-5) M), K+ (30 mM) induced relaxation of the trachealis muscle. The relaxation to K+ was not blocked by ouabain (10(-6) M), propranolol (10(-6) M), or indomethacin (10(-6) M). A relaxation in response to K+ was also observed in Ca2+-free solution, (with tone induced by methacholine), an effect not blocked by propranolol or ouabain. Tetraethylammonium (30 mM) (TEA), which ordinarily evokes contractile responses, induced trachealis relaxation in the presence of verapamil or nifedipine. The relaxation was unaltered by ouabain or propranolol. Tetrodotoxin (10(-6) M) (TTX) blocked 65% of the K+-induced relaxation in the presence of nifedipine and 100% of K+-induced relaxation either in a Ca2+-free solution or after polyamine exposure. TTX was without effect on TEA-induced relaxation after Ca2+-entry blocking drugs. Atropine (10(-6) M) or hexamethonium (10(-6) M) did not affect K+-induced relaxation after polyamine exposure. The concentration-response curve for K+-induced contraction in normal modified Krebs-Henseleit solution was shifted to the left by TTX. 8 It is concluded: (a) K+ has a direct effect on the trachealis causing contraction and an indirect effect, mediated by neurotransmitter release, causing relaxation. This latter effect is exposed when the direct effect is inhibited by Ca2+-entry blocking drugs, Ca2+-free solution or polyamine exposure; the indirect effect is non-adrenergic, non-cholinergic and not via ganglionic transmission; (b) the TEAinduced relaxation and a component of the K+-induced relaxation after Ca2+ blocking drugs cannot be explained by neurotransmitter release; (c) polyamines may act as naturally occurring Ca2+ antagonists.
我们之前观察到，在豚鼠离体气管接触多胺后，钾离子（K⁺）会产生矛盾的舒张效应。本研究的目的是评估这种舒张是否涉及细胞外钙离子（Ca²⁺）内流的减少。因此，我们研究了在存在Ca²⁺内流阻断药物以及无Ca²⁺溶液的情况下K⁺的作用。在硝苯地平（10⁻⁵ M）、维拉帕米（10⁻⁵ M）或地尔硫䓬（10⁻⁵ M）存在时，K⁺（30 mM）可诱导气管平滑肌舒张。对K⁺的舒张作用不受哇巴因（10⁻⁶ M）、普萘洛尔（10⁻⁶ M）或吲哚美辛（10⁻⁶ M）的阻断。在无Ca²⁺溶液中（由乙酰甲胆碱诱导张力）也观察到了对K⁺的舒张反应，该效应不受普萘洛尔或哇巴因的阻断。通常会引起收缩反应的四乙铵（30 mM）（TEA），在维拉帕米或硝苯地平存在时可诱导气管舒张。该舒张不受哇巴因或普萘洛尔的影响。河豚毒素（10⁻⁶ M）（TTX）在硝苯地平存在时可阻断65%的K⁺诱导的舒张，在无Ca²⁺溶液中或多胺暴露后可阻断100%的K⁺诱导的舒张。在Ca²⁺内流阻断药物作用后，TTX对TEA诱导的舒张无影响。阿托品（10⁻⁶ M）或六甲铵（10⁻⁶ M）在多胺暴露后不影响K⁺诱导的舒张。在正常改良的克雷布斯 - 亨塞尔特溶液中，TTX使K⁺诱导收缩的浓度 - 反应曲线向左移动。8 得出以下结论：（a）K⁺对气管有直接作用导致收缩，也有间接作用，通过神经递质释放介导导致舒张。当直接作用被Ca²⁺内流阻断药物、无Ca²⁺溶液或多胺暴露抑制时，后一种作用就会显现出来；间接作用是非肾上腺素能、非胆碱能且不通过神经节传递；（b）Ca²⁺阻断药物作用后，TEA诱导的舒张和K⁺诱导舒张的一部分不能用神经递质释放来解释；（c）多胺可能作为天然存在的Ca²⁺拮抗剂起作用。
