Advenier C, Naline E, Renier A
Br J Pharmacol. 1986 May;88(1):33-9. doi: 10.1111/j.1476-5381.1986.tb09468.x.
The effects of Bay K 8644, a dihydropyridine which increases calcium flux through the potential-operated channels were studied on the contractions induced by histamine, acetylcholine, KCl and Ca2+ on human isolated bronchial strips and the results were compared to those obtained on guinea-pig isolated tracheal spirals. Subsequently the contractant effects of Bay K 8644 in K+-enriched medium and in the presence of Ca2+ 0.03 mM were investigated. In Krebs normal calcium medium, Bay K 8644 did not significantly modify the EC50 of acetylcholine or histamine on the human bronchus, but in concentrations of 10(-7)-10(-6)M it potentiated the effects of KCl on that preparation. It did not modify the EC50 of acetylcholine, histamine or KCl on the guinea-pig trachea. In Ca2+-free Krebs medium with additional K+ (30 mM), Ca2+ concentration-response curves were displaced to the left by Bay K 8644 in the two preparations. Shifts were 0.52 +/- 0.11 and 0.72 +/- 0.16 log units respectively with Bay K 8644 10(-8) and 10(-7) M on human bronchus (n = 4) and 0.67 +/- 0.16 and 1.06 +/- 0.19 log units respectively with Bay K 8644 10(-7) and 10(-6) M on the guinea-pig trachea (n = 5). In Krebs medium with Ca2+ 0.03 mM and K+ 30 mM, Bay K 8644 (10(-8) to 10(-6) M) contracted both the human bronchus and the guinea-pig isolated trachea. This effect was competitively antagonized by nicardipine. 5 These results demonstrate the presence of dihydropyridine sites of action on human bronchus and confirm the minor role played by Ca2+ influx through potential-operated channels in the contractile effects of acetylcholine or histamine. They also demonstrate the similar reactivity of human bronchus and guinea-pig isolated trachea to Bay K 8644.
研究了二氢吡啶 Bay K 8644 对组胺、乙酰胆碱、氯化钾和钙离子引起的人离体支气管条收缩的影响，该物质可增加通过电压门控通道的钙内流，并将结果与在豚鼠离体气管螺旋条上获得的结果进行比较。随后，研究了 Bay K 8644 在高钾培养基中以及在 0.03 mM 钙离子存在下的收缩作用。在 Krebs 正常钙培养基中，Bay K 8644 并未显著改变乙酰胆碱或组胺对人支气管的半数有效浓度（EC50），但在 10(-7)-10(-6)M 的浓度下，它增强了氯化钾对该标本的作用。它并未改变乙酰胆碱、组胺或氯化钾对豚鼠气管的 EC50。在无钙的 Krebs 培养基中添加额外的钾（30 mM）时，Bay K 8644 使两种标本中钙离子浓度-反应曲线向左移动。在人支气管上，Bay K 8644 10(-8) 和 10(-7) M 时的位移分别为 0.52±0.11 和 0.72±0.16 对数单位（n = 4）；在豚鼠气管上，Bay K 8644 10(-7) 和 10(-6) M 时的位移分别为 0.67±0.16 和 1.06±0.19 对数单位（n = 5）。在含有 0.03 mM 钙离子和 30 mM 钾的 Krebs 培养基中，Bay K 8644（10(-8) 至 10(-6) M）使人类支气管和豚鼠离体气管均发生收缩。这种作用被尼卡地平竞争性拮抗。这些结果证明了人支气管上存在二氢吡啶作用位点，并证实了通过电压门控通道的钙内流在乙酰胆碱或组胺收缩作用中所起的次要作用。它们还证明了人支气管和豚鼠离体气管对 Bay K 8644 具有相似的反应性。
