Christophe J P, Frandsen E K, Conlon T P, Krishna G, Gardner J D
J Biol Chem. 1976 Aug 10;251(15):4640-5.
The COOH-terminal octapeptide of cholecystokinin (CCK-OP) and carbamylcholine each increased calcium outflux, cellular cyclic GMP and amylase secretion in dispersed guinea pig pancreatic acinar cells. Following addition of CCK-OP or carbamylcholine, cellular cyclic GMP increased as early as 15 s, became maximal after 1 to 2 min, and then decreased steadily during the subsequent incubation. For both CCK-OP and carbamylcholine there was close agreement between the dose-response curve for stimulation of calcium outflux and that for increase of cellular cyclic GMP. With CCK-OP an effect on both functions could be detected at 10(-10) M and maximal stimulation occurred at 3 X 10(-8) M. With carbamylcholine an effect on both functions could be detected at 10(-5) M and maximal stimulation occurred at 3 X 10(-3) M. Atropine inhibited stimulation of both cyclic GMP and calcium outflux by carbamylcholine but not by CCK-OP. Stimulation of calcium outflux or cellular cyclic GMP by CCK-OP or carbamylcholine did not require extracellular calcium since stimulation occurred in a calcium-free, ethylene glycol bis(beta, beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA)-containing solution. The divalent cation ionophore A-23187 increased bidirectional fluxes of calcium, cellular cyclic GMP and secretion of amylase from dispersed pancreatic acinar cells. Like CCK-OP and carbamylcholine, the ionophore stimulated calcium outflux and cellular cyclic GMP in a calcium-free, EGTA-containing solution. These results suggest that in pancreatic acinar cells the initial step in the sequence of events mediating the action of ionophore as well as that of CCK-OP and carbamylcholine is stimulation of calcium outflux, and that this stimulation then increases cellular cyclic GMP.
胆囊收缩素的羧基末端八肽（CCK-OP）和氨甲酰胆碱均可增加豚鼠分散胰腺腺泡细胞的钙外流、细胞内环鸟苷酸（cGMP）水平及淀粉酶分泌。加入CCK-OP或氨甲酰胆碱后，细胞内cGMP最早在15秒时升高，1至2分钟后达到峰值，随后在后续孵育过程中稳步下降。对于CCK-OP和氨甲酰胆碱，刺激钙外流的剂量反应曲线与细胞内cGMP增加的剂量反应曲线密切一致。对于CCK-OP，在10⁻¹⁰ M时可检测到对两种功能的影响，最大刺激出现在3×10⁻⁸ M。对于氨甲酰胆碱，在10⁻⁵ M时可检测到对两种功能的影响，最大刺激出现在3×10⁻³ M。阿托品可抑制氨甲酰胆碱对cGMP和钙外流的刺激，但不抑制CCK-OP的刺激。CCK-OP或氨甲酰胆碱刺激钙外流或细胞内cGMP并不需要细胞外钙，因为在不含钙的、含有乙二醇双（β，β-氨基乙基醚）N，N'-四乙酸（EGTA）的溶液中也能发生刺激。二价阳离子载体A-23187可增加分散胰腺腺泡细胞钙的双向通量、细胞内cGMP水平及淀粉酶分泌。与CCK-OP和氨甲酰胆碱一样，该载体在不含钙的、含有EGTA的溶液中也能刺激钙外流和细胞内cGMP。这些结果表明，在胰腺腺泡细胞中，介导载体以及CCK-OP和氨甲酰胆碱作用的事件序列的初始步骤是刺激钙外流，然后这种刺激会增加细胞内cGMP。
