Permanent photodynamic activation of the cholecystokinin 2 receptor
Permanent photodynamic activation of the cholecystokinin 2 receptor
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胆囊收缩素 2 受体的永久光动力激活
DOI：
10.3390/biom10020236
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发表时间：
2020-02
期刊：
影响因子：
5.5
通讯作者：
Cui ZJ
中科院分区：
文献类型：
--
作者：
Tang WZ;Cui ZJ
胆囊收缩素2受体（Cholecystokinin 2 receptor，CCK 2 R）在中枢神经系统和外周组织中表达，在高级神经和胃肠道功能、疼痛感觉和肿瘤生长中起重要作用。胆囊收缩素或胃泌素可逆地激活CCK 2 R，但它是否可以永久激活尚不清楚。在这项工作中，我们发现CHO-K1细胞中表达的CCK 2 R在黑暗中被磺化铝酞菁（SALPC /AlPcS 4，10 - 1 000 nM）永久激活，如Fura-2荧光钙成像所监测的。还观察到AlPcS 2而非PcS 4的永久性CCK 2 R活化。CCK 2 R预先暴露于SALPC（3，10 nM），随后通过光照射（> 580 nm，31.5 mW·cm-2）敏化。将光敏蛋白miniSOG与CCK 2 R N端融合后，在CHO K1细胞中表达，450 nm，85 mW·cm-2的光照射可激活CCK 2 R（miniSOG CCK 2 R），CCK 2 R拮抗剂YM 022（30 nM）可阻断miniSOG的激活。从这些数据可以得出结论，SALPC是一种在黑暗中持久的CCK 2 R激动剂，CCK 2 R被miniSOG作为光敏剂永久地光遗传激活。SALPC和CCK 2 R的这些性质可用于研究CCK 2 R的生理学，并可能用于疼痛和癌症的治疗。
Cholecystokinin 2 receptor (CCK2R) is expressed in central nervous system and peripheral tissues, plays important roles in higher nervous and gastrointestinal functions, in pain sensation and cancer growth. CCK2R is reversibly activated by cholecystokinin or gastrin but whether it could be activated permanently is not known. In this work we found that CCK2R expressed in CHO-K1 cells was permanently activated in the dark by sulphonated aluminum phthalocyanine (SALPC / AlPcS4, 10 - 1 000 nM) as monitored by Fura-2 fluorescent calcium imaging. Permanent CCK2R activation was also observed with AlPcS2 but not PcS4. CCK2R previously exposed to SALPC (3, 10 nM) were sensitized by subsequent light irradiation (> 580 nm, 31.5 mW•cm-2). After genetically encoded protein photosensitiser miniSOG was fused to N-terminus of CCK2R and expressed in CHO-K1 cells, light irradiation (450 nm, 85 mW•cm-2) activated in-frame CCK2R (miniSOG-CCK2R) permanently triggering persistent calcium oscillations blocked by CCK2R antagonist YM 022 (30 nM). From these data it is concluded that SALPC is a long-lasting CCK2R agonist in the dark, CCK2R is photogenetically activated permanently with miniSOG as photosensitiser. Such properties of SALPC and CCK2R could be used to study CCK2R physiology and possibly for therapy of pain and cancer.
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DOI：
10.1254/jjp.75.33
发表时间：
1997-09
期刊：
Japanese journal of pharmacology
影响因子：
--
作者：
K. Akagi;T. Nagao;T. Urushidani
通讯作者：
K. Akagi;T. Nagao;T. Urushidani
影响因子：
6.3
作者：
K. Miyasaka;M. Ohta;S. Kanai;Y. Yoshida;Norikazu Sato;A. Nagata;T. Matsui;T. Noda;A. Jimi;S. Takiguchi;Y. Takata;T. Kawanami;A. Funakoshi
通讯作者：
K. Miyasaka;M. Ohta;S. Kanai;Y. Yoshida;Norikazu Sato;A. Nagata;T. Matsui;T. Noda;A. Jimi;S. Takiguchi;Y. Takata;T. Kawanami;A. Funakoshi
影响因子：
7.3
作者：
B. Charpentier;C. Durieux;I. Menant;B. Roques
通讯作者：
B. Charpentier;C. Durieux;I. Menant;B. Roques
影响因子：
9.2
作者：
Smith JP;Fonkoua LK;Moody TW
通讯作者：
Moody TW
卟啉和邻苯烷在光动力疗法，成像和疗法学中的独特诊断和治疗作用。
影响因子：
12.4
作者：
Josefsen LB;Boyle RW
通讯作者：
Boyle RW