Matran R, Naline E, Advenier C, Lockhart A, Tricot J F, Regoli D
Faculté de Médecine Cochin-Port-Royal, Laboratoire d'Explorations Fonctionnelles Respiratoires, Paris, France.
Fundam Clin Pharmacol. 1988;2(1):47-55. doi: 10.1111/j.1472-8206.1988.tb00620.x.
Whether the influx of calcium through voltage-operated channels is involved in the stimulatory effects of substance P and neurokinin A in airways smooth muscle is not yet firmly established. This question was addressed in the present study using guinea pig trachea and human bronchi suspended in normal or calcium-free Krebs solution and tested with inhibitors of calcium channels. In calcium-free Krebs solution, the myotropic effects of substance P (10(-7) M), neurokinin A (3.10(-8) M), acetylcholine (2.10(-5) M), and histamine (2.10(-5) M) were reduced by 27-57%, while those of potassium chloride and tetraethylammonium were practically abolished. Calcium antagonists such as verapamil or nicardipine, when applied at concentrations of 10(-8)-10(-6) M, inhibited the contractions produced by potassium chloride and tetraethylammonium, whereas higher concentrations (10(-5)-10(-4) M) of both inhibitors were needed to reduce the effects of substance P, neurokinin A, acetylcholine, and histamine. In neither preparation did the calcium agonist Bay K 8644 (10(-6) M) modify the effects of neurokinin A, substance P, acetylcholine, or histamine, but it potentiated potassium chloride's effect on human bronchi. We conclude that transmembrane calcium influx through voltage-operated channels plays a minor role in the stimulatory effects of neurokinins in airways smooth muscle.
通过电压门控通道的钙内流是否参与P物质和神经激肽A对气道平滑肌的刺激作用，目前尚未完全明确。本研究利用豚鼠气管和人支气管，将其置于正常或无钙的克雷布斯溶液中，并使用钙通道抑制剂进行检测，以探讨这一问题。在无钙的克雷布斯溶液中，P物质（10⁻⁷M）、神经激肽A（3×10⁻⁸M）、乙酰胆碱（2×10⁻⁵M）和组胺（2×10⁻⁵M）的肌otropic效应降低了27% - 57%，而氯化钾和四乙铵的效应几乎完全消失。钙拮抗剂如维拉帕米或尼卡地平，当以10⁻⁸ - 10⁻⁶M的浓度应用时，可抑制氯化钾和四乙铵引起的收缩，而两种抑制剂需要更高的浓度（10⁻⁵ - 10⁻⁴M）才能降低P物质、神经激肽A、乙酰胆碱和组胺的效应。在这两种制剂中，钙激动剂Bay K 8644（10⁻⁶M）均未改变神经激肽A、P物质、乙酰胆碱或组胺的效应，但它增强了氯化钾对人支气管的作用。我们得出结论，通过电压门控通道的跨膜钙内流在神经激肽对气道平滑肌的刺激作用中起次要作用。
