Matthijs G, Himpens B, Peeters T L, Vantrappen G
Department of Medical Research, University of Leuven, Belgium.
Am J Physiol. 1990 Jul;259(1 Pt 1):C150-60. doi: 10.1152/ajpcell.1990.259.1.C150.
In intact sheets of the guinea pig ileal longitudinal muscle, loaded with fura-2, both substance P (SP)- and K(+)-induced contractile responses are preceded by cytoplasmic free Ca2+ ([Ca2+]i) variations. In response to SP (10(-10)-10(-7) M), [Ca2+]i and force increased concentration dependently. From 10(-9) M on, the response was biphasic: an initial Ca2+ spike and force transient were followed by a tonic component. The [Ca2+]i and force vs. log [SP] curves were sigmoidal for the initial phasic component, while a homologous receptor desensitization caused a reduced tonic component of the [Ca2+]i and contractile response at higher concentrations of SP. Both intracellular Ca2+ release and Ca2+ influx play a role in the effect of the peptide. In depolarizing solutions (140 mM K+) and in Ca2(+)-free medium (2 mM EGTA), SP induced a transient increase in [Ca2+]i and force. The Ca2+ stores used by SP and acetylcholine (ACh) overlap. [Ca2+]i and force fell to base-line levels when the extracellular Ca2+ was reduced from 1.2 to 0.2 mM during stimulation with SP. Verapamil reduced the tonic response. We also studied the relation between [Ca2+]i and force for the peak and steady-state values after stimulation with increasing concentrations of SP and K+. The phasic force response was linearly related to log [Ca2+]i. During the sustained response to K+, the Ca2+ sensitivity of the contractile/regulatory proteins was decreased, whereas no changes were observed during prolonged stimulation with the peptide.
在装载有fura-2的豚鼠回肠纵行肌完整薄片中，P物质（SP）和K⁺诱导的收缩反应之前均有细胞质游离Ca²⁺（[Ca²⁺]i）变化。对SP（10⁻¹⁰ - 10⁻⁷ M）的反应中，[Ca²⁺]i和张力浓度依赖性增加。从10⁻⁹ M起，反应呈双相：初始的Ca²⁺尖峰和张力瞬变之后是强直成分。对于初始的相性成分，[Ca²⁺]i和张力与log [SP]曲线呈S形，而同源受体脱敏导致在较高浓度SP时[Ca²⁺]i和收缩反应的强直成分降低。细胞内Ca²⁺释放和Ca²⁺内流在该肽的作用中均起作用。在去极化溶液（140 mM K⁺）和无Ca²⁺培养基（2 mM EGTA）中，SP诱导[Ca²⁺]i和张力短暂增加。SP和乙酰胆碱（ACh）使用的Ca²⁺储存库重叠。在用SP刺激期间，当细胞外Ca²⁺从1.2 mM降至0.2 mM时，[Ca²⁺]i和张力降至基线水平。维拉帕米降低了强直反应。我们还研究了用递增浓度的SP和K⁺刺激后[Ca²⁺]i与峰值和稳态值时张力之间的关系。相性张力反应与log [Ca²⁺]i呈线性相关。在对K⁺的持续反应期间，收缩/调节蛋白的Ca²⁺敏感性降低，而在用该肽长时间刺激期间未观察到变化。
