已知光动力作用所产生的单线态氧特异性激活大鼠胰腺腺泡细胞CCK1型受体，引发非配体介导持续性胞浆钙振荡。但单线态氧如何激活CCK1型受体，并不清楚。本论文研究在新鲜分离的大鼠胰腺腺泡细胞中，甲硫氨酸和半胱氨酸特异性氧化剂Ch-t、PCMB、DTNB、MTSEA对CCK1型受体所介导的胞浆钙振荡的影响。研究结果显示，无论CCK1型受体是否处于激活状态，低浓度Ch-t (1, 3, 10, 30 M)都浓度依赖性抑制受体活性；而高浓度Ch-t (100 M)作用10 min，可引发高台上非持续胞浆钙振荡。高浓度Ch-t (100M)所引发的钙振荡可被CCK1型受体抑制剂FK480所抑制，因而是由CCK1型受体所介导的，在一定程度上模拟了光动力作用。DTT (2 mM) 与Ch-t共同作用的实验表明，半胱氨酸的氧化对CCK1型受体的激活具有重要作用。由于Ch-t是甲硫氨酸/半胱氨酸的双靶氧化剂，在进一步的试验中研究了半胱氨酸特异性氧化剂PCMB、DTNB、MTSEA的作用。研究发现低浓度PCMB(1, 5, 10, 25 M)可浓度依赖性抑制CCK1型受体，该抑制作用可被DTT部分恢复；高浓度PCMB (50, 100 M)本身引发高台上的持续胞浆钙振荡，但CCK1受体或M3受体抑制剂对此持续性钙振荡没有抑制作用。MTSEA、DTNB则只在受体处于激活状态时部分、可逆抑制CCK1受体；作用于未被激活的受体时，则对受体活性无影响。综上所述，低浓度Ch-t仅氧化Cys后抑制CCK1受体，该结论与半胱氨酸特异性氧化剂结果一致。CCK1受体Cys94的氧化可能参与了这一过程。高浓度Ch-t氧化更多半胱氨酸，导致受体构型发生改变，可能使原本埋藏在跨膜结构域的其他氨基酸暴露出来并被氧化，从而引发胞浆钙振荡。这一过程可能有位于第三跨膜区域的Met121的参与。但是Ch-t氧化所引发的细胞反应与半胱氨酸特异性氧化剂所引发的反应并不完全一致，间接证明Ch-t的反应中有甲硫氨酸氧化的参与。这些结果对于阐明光动力作用对CCK1受体的激活具有重要意义。

Previous works have found that photodynamically-generated singlet oxygen selectively and permanently activates CCK1 receptor in rat pancreatic acini, but the detailed mechanism for such activation is unclear. Small molecule oxidants oxidizing cysteines and methionines could potentially help elucidate this photodynamic action mechanism. The aim of the present work therefore was to investigate effects of methionine and cysteine oxidation on CCK1 receptor-triggered cytosolic calcium oscillations. The cell membrane non-permeant sulfhydryl oxidants chloramine-t (Ch-t), p-chloromercuribenzoate (pCMB), 2-aminoethyl methanethiosulfonate hydrobromide(MTSEA), 5,5-dithiobis(2-nitrobenzoic acid) (DNTB) were used. It was found that low Ch-t concentrations (1, 3, 10, 30M) inhibited CCK1 receptor activation in concentration-dependently, whether CCK1 receptor was activated or not; at the higher concentration of 100M Ch-t triggered transient cytosolic calcium oscillations on an elevated baseline, the calcium spikes disappeared if the CCK1 receptor blocker FK480 was present, therefore Ch-t partially mimicked photodynamic action. When DTT 2 mM was also present, Ch-t no longer had such effects, indicating that cysteine oxidation was involved in CCK1 receptor activation. In contrast to the methionine/cysteine oxidant Ch-t, the cysteine oxidants PCMB, DTNB, MTSEA showed different effects. Low concentrations of PCMB (1, 5, 10, 25 M) inhibited CCK-triggered calcium oscillations concentration-dependently, similar to low concentrations of Ch-t, this inhibition were partially reversed by DTT. Higher PCMB concentrations (50, 100M）induced long-lasting calcium oscillations over an elevated baseline, which were not inhibited by either CCK1 receptor blocker FK 480 or by the muscarinic cholinergic blocker atropine. Low concentrations of MTSEA and DTNB reversiblly inhibited CCK1 receptor in activated state, but had no effect on unstimulated CCK1 receptors. Therefore low Ch-t concentrations inhibited CCK1 receptor by oxidizing cysteine, which is consistent with data obtained with the cysteine oxidants, Cys94 may be involved in this process. Ch-t at the higher concentration of 100 M may induce oxidation on more cysteine residues, inducing receptor conformational changes and exposing and oxidizing deep-embedded methionine residues, to trigger calcium oscillations, Met121 may be involved in this process. The differences between Ch-t and cysteine-specific oxidants suggest that methionine oxidation is important for photodynamic activation of CCK1 receptor in rat pancreatic acinar cells.