Both low- and high-affinity CCK receptor states mediate trophic effects on rat pancreatic acinar cells.
Both low- and high-affinity CCK receptor states mediate trophic effects on rat pancreatic acinar cells.
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低亲和力和高亲和力 CCK 受体状态均介导对大鼠胰腺腺泡细胞的营养作用。
DOI：
10.1152/ajpgi.1993.265.6.g1177
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Logsdon,CD
中科院分区：
文献类型：
--
作者：
Hoshi,H;Logsdon,CD
胆囊收缩素（CCK）刺激胰腺腺泡细胞的生长。然而，这种营养作用所涉及的分子机制尚不清楚。CCK结合高亲和力和低亲和力受体状态，这两种状态似乎激活不同的细胞内信使，并对淀粉酶释放产生相反的影响。JMV-180是一种CCK类似物，在大鼠中以高亲和力状态作为激动剂，以低亲和力状态作为拮抗剂相互作用。在本研究中，CCK八肽（CCK-8）和JMV-180的能力，以刺激大鼠胰腺腺泡细胞在原代培养中的生长进行了测试。CCK-8以剂量依赖性方式刺激[3 H]胸苷掺入DNA。在0.3 nM时观察到效果，在3 nM CCK-8时观察到最大增加（对照组的442 +/- 53%，n = 5，P < 0.01）。JMV-180还刺激DNA合成。用10 nM观察到效果，并且通过100 nM JMV-180刺激对照的267 +/-82%（n = 4，P < 0.01）的最大增加。JMV-180的这些数据表明CCK的高亲和力受体状态能够刺激DNA合成。然而，在同一实验中，CCK的效果总是显著大于JMV-180的效果。为了测试CCK是否通过与低亲和力状态的相互作用具有额外的作用，检查了JMV-180与最大剂量的CCK-8的组合的作用。JMV-180以剂量依赖性方式抑制CCK-8的最大效应，最大抑制作用发生在1 μ M JMV-180时。3 nM CCK-8和1 μ M JMV-180的组合的作用不大于单独的JMV-180的作用。综上所述，这些数据表明，CCK介导的大鼠胰腺腺泡细胞在体外DNA合成的增加发生的相互作用与高和低亲和力受体状态。
Cholecystokinin (CCK) stimulates the growth of pancreatic acinar cells. However, the molecular mechanisms involved in this trophic action are unknown. CCK binds to both high- and low-affinity receptor states, and these two states appear to activate separate sets of intracellular messengers and have opposite effects on amylase release. JMV-180 is a CCK analogue that interacts in the rat with the high-affinity state as an agonist and the low-affinity state as an antagonist. In the current study, CCK octapeptide (CCK-8) and JMV-180 were tested for their ability to stimulate the growth of rat pancreatic acinar cells in primary culture. CCK-8 stimulated [3H]thymidine incorporation into DNA in a dose-dependent manner. Effects were observed with 0.3 nM, and maximal increases were seen at 3 nM CCK-8 (442 +/- 53% of control, n = 5, P < 0.01). JMV-180 also stimulated DNA synthesis. Effects were noted with 10 nM, and a maximal increase of 267 +/- 82% (n = 4, P < 0.01) of control was stimulated by 100 nM JMV-180. These data with JMV-180 indicate that the high-affinity receptor state for CCK is capable of stimulating DNA synthesis. However, within the same experiment the effects of CCK were always significantly greater than those of JMV-180. To test whether CCK has an additional effect through interactions with the low-affinity state, the effects of a combination of JMV-180 with a maximal dose of CCK-8 were examined. JMV-180 inhibited the maximal effect of CCK-8 in a dose-dependent manner with a maximal inhibition occurring with 1 microM JMV-180. The effects of the combination of 3 nM CCK-8 and 1 microM JMV-180 were no greater than those of JMV-180 alone. Taken together these data indicate that CCK-mediated increases in DNA synthesis in rat pancreatic acinar cells in vitro occur by interactions with both high- and low-affinity receptor states.