Kimura I, Kimura M, Nakayama N, Kimura M
Arch Int Pharmacodyn Ther. 1983 Oct;265(2):320-34.
The mechanisms by which cholecystokinin (CCK)-C-terminal peptides relax biliary smooth muscles were investigated using circular and longitudinal muscles of hog bile duct ampulla. In normal Tyrode's solution the concentration-contraction curves for acetylcholine (ACh) were in a higher range in circular muscle than in longitudinal muscle. In K+-depolarized muscles the concentration-contraction curves for Ca2+ were in a lower range in circular than in longitudinal muscle. When the Ca2+ concentration in Tyrode's solution was decreased, circular muscle showed concentration-dependent relaxation of normal tone from 1.8 mM to zero calcium, but longitudinal muscle did not show any relaxation. Concentrations of CCK-4, CCK-6 and CCK-7 producing 50% relaxation of normal tone in circular muscles were 19 microM, and 53 nM, respectively; concentrations producing 50% inhibition of ACh-induced contraction in longitudinal muscle were 20, 13 and 47 microM, respectively. The effects of calcium removal on the membrane potential were hyperpolarization in circular muscle but depolarization in longitudinal muscle, although there was cessation of calcium spikes in both muscles. In longitudinal muscle, CCK-4 suppressed spontaneous spikes and evoked spikes. In circular muscle, CCK-4 did not suppress evoked spikes even in a concentration that caused relaxation and hyperpolarization of the membrane. In conclusion, CCK-C-terminal peptides may induce relaxation of circular muscle, not by direct suppression of calcium influx during the action potential, but by intracellular decrease in Ca2+ levels probably arising from increased calcium uptake into the sarcoplasmic reticulum or the plasma membrane. On the other hand, the peptides do not induce relaxation of longitudinal muscle, but suppress only the calcium influx (resulting in cessation of spontaneous contraction). Therefore, CCK-4 may cause a relaxation of normal tone in circular muscle, and an inhibition in the spontaneous contraction, induced by some transmitters, of longitudinal muscle.
利用猪胆管壶腹的环形肌和纵行肌，研究了胆囊收缩素（CCK）-C末端肽舒张胆道平滑肌的机制。在正常的台氏液中，乙酰胆碱（ACh）的浓度-收缩曲线在环形肌中的范围高于纵行肌。在K⁺去极化的肌肉中，Ca²⁺的浓度-收缩曲线在环形肌中的范围低于纵行肌。当台氏液中的Ca²⁺浓度降低时，环形肌表现出浓度依赖性的正常张力舒张，从1.8 mM降至零钙，但纵行肌未表现出任何舒张。使环形肌正常张力产生50%舒张的CCK-4、CCK-6和CCK-7的浓度分别为19 μM、53 nM；使纵行肌中ACh诱导的收缩产生50%抑制的浓度分别为20、13和47 μM。去除钙对膜电位的影响在环形肌中是超极化，但在纵行肌中是去极化，尽管两种肌肉中的钙峰均停止。在纵行肌中，CCK-4抑制自发峰和诱发峰。在环形肌中，即使在引起膜舒张和超极化的浓度下，CCK-4也不抑制诱发峰。总之，CCK-C末端肽可能不是通过直接抑制动作电位期间的钙内流，而是通过细胞内Ca²⁺水平的降低来诱导环形肌舒张，这种降低可能是由于肌浆网或质膜对钙的摄取增加所致。另一方面，这些肽不诱导纵行肌舒张，而仅抑制钙内流（导致自发收缩停止）。因此，CCK-4可能导致环形肌正常张力的舒张，并抑制纵行肌由某些递质诱导的自发收缩。
