Gardner J D, Conlon T P, Kleveman H L, Adams T D, Ondetti M A
J Clin Invest. 1975 Aug;56(2):366-75. doi: 10.1172/JCI108101.
COOH-terminal octapeptide of cholecystokinin (CCK-octapeptide) and the cholinergic agent carbamylcholine each produced a fourfold stimulation of calcium outflux in guinea pig isolated pancreatic acinar cells. Neither agent altered calcium influx. Stimulation of calcium outflux was rapid and specific, was abolished by reducing the incubation temperature to 4 degrees C, and was a saturable function of the secretagogue concentration. The concentrations of CCK-octapeptide and carbamylcholine that produced half-maximal stimulation of calcium outflux were 3.1 x 10(-10) M and 4.9 x 10(-5) M, respectively. The cholinergic antagonist antropine competitively inhibited carbamylcholine stimulation of calcium outflux but did not alter stimulation produced by CCK-octapeptide. Stimulation of calcium outflux by maximal concentrations of carbamycholine plus CCK-octapeptide was the same as that produced by a maximal concentration of either agent alone.Calcium outflux became refractory to stimulation by secretagogues, and incubation with either CCK-ostapeptide or carbamylcholine produced a refractoriness to both agents. The relative potencies with CCK and its related fragments stimulated calcium outflux were CCK-octapeptide greater than heptapeptide greater than CCK greater than hexapeptide = gastrin. Secretin, glucagon, and vasoactive intestinal peptide, at concentrations as high as 10(-5) M, failed to alter calcium outflux and did not affect stimulation by CCK-octapeptide or by carbamycholine.
胆囊收缩素的羧基末端八肽（CCK - 八肽）和胆碱能药物氨甲酰胆碱均可使豚鼠离体胰腺腺泡细胞的钙外流增加四倍。两种药物均未改变钙内流。钙外流的刺激迅速且具有特异性，将孵育温度降至4℃可消除该刺激，且是促分泌素浓度的饱和函数。产生半数最大钙外流刺激的CCK - 八肽和氨甲酰胆碱浓度分别为3.1×10⁻¹⁰ M和4.9×10⁻⁵ M。胆碱能拮抗剂阿托品竞争性抑制氨甲酰胆碱对钙外流的刺激，但不改变CCK - 八肽产生的刺激。最大浓度的氨甲酰胆碱加CCK - 八肽对钙外流的刺激与单独使用最大浓度的任何一种药物产生的刺激相同。钙外流对促分泌素的刺激变得不应期，用CCK - 八肽或氨甲酰胆碱孵育会导致对两种药物均产生不应期。CCK及其相关片段刺激钙外流的相对效力为：CCK - 八肽＞七肽＞CCK＞六肽 = 胃泌素。促胰液素、胰高血糖素和血管活性肠肽在高达10⁻⁵ M的浓度下未能改变钙外流，也不影响CCK - 八肽或氨甲酰胆碱所致的刺激。
