Kachur J F, Phillips G S, Gaginella T S
NOVA Pharmaceutical Corporation, Baltimore, Maryland.
Gastroenterology. 1991 Feb;100(2):344-9. doi: 10.1016/0016-5085(91)90201-u.
We examined the effect of cholecystokinin octapeptide on electrolyte transport across isolated guinea pig mucosa. Segments of distal ileum stripped of longitudinal muscle and bathed on both sides with a Krebs'-bicarbonate buffer responded to cholecystokinin octapeptide when studied under short-circuited conditions. Cholecystokinin octapeptide (0.5-50 nmol/L) evoked a transient (4-10-minute) increase in transepithelial potential difference and short-circuit current upon application to the serosal side. Maximal increases in short-circuit current, achieved at 50-500 nmol/L, were 67 +/- 11 microA/cm2, whereas half-maximal effects occurred at a concentration of 0.7 +/- 0.2 nmol/L. Pretreatment of the tissues with 0.5 mumol/L atropine reduced the maximal short-circuit response to cholecystokinin octapeptide by 53%. The change in short-circuit current due to cholecystokinin octapeptide was nearly abolished by pretreatment with 0.5 mumol/L tetrodotoxin, suggesting neuronal involvement. Cholecystokinin octapeptide-induced increases in short-circuit current were halved by removal of serosal buffer Ca2+ and were abolished in Cl(-)- and HCO3(-)-free buffer. The cholecystokin-receptor antagonists proglumide and lorglumide shifted the concentration-response curve for cholecystokinin octapeptide competitively to the right, having antagonists potencies of 130 and 0.03 mumol/L, respectively. Cerulein (0.1-500 nmol/L) also increased short-circuit current, whereas nonsulfated cholecystokinin octapeptide was ineffective. In conclusion, cholecystokinin octapeptide seems to act at neuronal cholecystokinin receptors to stimulate mucosal anion secretion, in part, by releasing acetylcholine.
我们研究了八肽胆囊收缩素对豚鼠离体黏膜电解质转运的影响。去除纵行肌的回肠末端节段，在短路条件下进行研究时，两侧均用 Krebs - 碳酸氢盐缓冲液灌注，对八肽胆囊收缩素产生反应。将八肽胆囊收缩素（0.5 - 50 nmol/L）应用于浆膜侧时，可引起跨上皮电位差和短路电流短暂（4 - 10 分钟）增加。在 50 - 500 nmol/L 时短路电流达到最大增加，为 67±11 μA/cm²，而半数最大效应发生在浓度为 0.7±0.2 nmol/L 时。用 0.5 μmol/L 阿托品预处理组织可使八肽胆囊收缩素的最大短路反应降低 53%。用 0.5 μmol/L 河豚毒素预处理几乎消除了八肽胆囊收缩素引起的短路电流变化，提示有神经元参与。去除浆膜缓冲液中的 Ca²⁺可使八肽胆囊收缩素诱导的短路电流增加减半，而在无 Cl⁻和无 HCO₃⁻的缓冲液中则完全消除。胆囊收缩素受体拮抗剂丙谷胺和氯谷胺将八肽胆囊收缩素的浓度 - 反应曲线竞争性地向右移动，拮抗剂效力分别为 130 和 0.03 μmol/L。雨蛙素（0.1 - 500 nmol/L）也增加短路电流，而非硫酸化的八肽胆囊收缩素则无效。总之，八肽胆囊收缩素似乎作用于神经元胆囊收缩素受体，部分通过释放乙酰胆碱来刺激黏膜阴离子分泌。
