更新于：2024-11-01

CCKA

更新于：2024-11-01

基本信息

别名

CCK-A receptor、CCK-AR、CCK1-R

+ [6]

简介

Receptor for cholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gastrin. It modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.

关联

项与 CCKA 相关的药物

Sincalide

辛卡利特

靶点

CCKA x CCKB

作用机制

CCKA激动剂 [+1]

在研机构

Maia Pharmaceuticals, Inc. [+1]

原研机构

Bracco International BV

在研适应症

胆囊疾病 [+3]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期1976-07-21

PNB-001

靶点

CCKA x CCKB

作用机制

CCKA拮抗剂 [+1]

在研机构

PNB Vesper Life Sciences Pvt. Ltd

原研机构

PNB Vesper Life Sciences Pvt. Ltd

在研适应症

新型冠状病毒感染 [+2]

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

Dexloxiglumide

靶点

CCKA

作用机制

CCKA拮抗剂

在研机构

Allergan Ltd. (Ireland)

原研机构

Rottapharm SpA

在研适应症

肠易激综合征

非在研适应症

消化不良 [+2]

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

项与 CCKA 相关的临床试验

CTRI/2022/10/046658 / Recruiting临床2期

A Phase II, Multicenter, Randomized, Double-blind, Placebo controlled Clinical study toevaluate efficacy and safety of PNB-001 as an adjunct to Mesalamine compared toMesalamine alone in Subjects with Inflammatory bowel disease

开始日期2022-10-28

申办/合作机构

PNB Vesper Life Sciences Pvt. Ltd

[+1]

CTRI/2021/09/036411 / Recruiting临床3期

A Phase III, Randomized, Open Label, Multicentric, Clinical Study to Evaluate the Efficacy and Safety of PNB-001 as an Adjunct to Standard of Care Compared to Standard of Care Alone in Treatment of Patients with Moderate COVID-19 Infection

开始日期2021-09-27

申办/合作机构

PNB Vesper Life Sciences Pvt. Ltd

CTRI/2020/10/028423 / Completed临床2期

A Randomized, Open label Clinical Study to Evaluate Efficacy and Safety of PNB-001 in Patients with moderate COVID-19 Infection.

开始日期2020-10-28

申办/合作机构

PNB Vesper Life Sciences Pvt. Ltd

[+1]

100 项与 CCKA 相关的临床结果

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100 项与 CCKA 相关的转化医学

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0 项与 CCKA 相关的专利（医药）

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1,080

项与 CCKA 相关的文献（医药）

2024-11-01·Neurology Neuroimmunology & Neuroinflammation

A Simple Score (MOG-AR) to Identify Individuals at High Risk of Relapse After MOGAD Attack

Article

作者: Fan, Moli ; Xu, Yun ; Tian, De-Cai ; Cong, Hengri ; Meng, Huaxing ; Sun, Jiali ; Song, Tian ; Zhang, Xinghu ; Feng, Jinzhou ; Yao, Yajun ; Yin, Linlin ; Shi, Fu-Dong ; Wang, Huabing ; Wei, Yuzhen ; Yang, Chun-Sheng

BACKGROUND AND OBJECTIVESTo identify predictors for relapse in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to develop and validate a simple risk score for predicting relapse.METHODSIn China National Registry of Neuro-Inflammatory Diseases (CNRID), we identified patients with MOGAD from March 2023 and followed up prospectively to September 2023. The primary endpoint was MOGAD relapse, confirmed by an independent panel. Patients were randomly divided into model development (75%) and internal validation (25%) cohorts. Prediction models were constructed and internally validated using Andersen-Gill models. Nomogram and relapse risk score were generated based on the final prediction models.RESULTSA total of 188 patients (comprising 612 treatment episodes) were included in cohorts. Female (HR: 0.687, 95% CI 0.524-0.899, p = 0.006), onset age 45 years or older (HR: 1.621, 95% CI 1.242-2.116, p < 0.001), immunosuppressive therapy (HR: 0.338, 95% CI 0.239-0.479, p < 0.001), oral corticosteroids >3 months (HR 0.449, 95% CI 0.326-0.620, p < 0.001), and onset phenotype (p < 0.001) were identified as factors associated with MOGAD relapse. A predictive score, termed MOG-AR (Immunosuppressive therapy, oral Corticosteroids, Onset Age, Sex, Attack phenotype), derived in prediction model, demonstrated strong predictive ability for MOGAD relapse. MOG-AR score of 13-16 indicates a higher risk of relapse (HR: 3.285, 95% CI 1.473-7.327, p = 0.004).DISCUSSIONThe risk of MOGAD relapse seems to be predictable. Further validation of MOG-AR score developed from this cohort to determine appropriate treatment and monitoring frequency is warranted.TRIAL REGISTRATION INFORMATIONCNRID, NCT05154370, registered December 13, 2021, first enrolled December 15, 2021.

2024-10-24·Journal of Bacteriology

The Sinorhizobium meliloti nitrogen-fixing symbiosis requires CbrA-dependent regulation of a DivL and CckA phosphorelay

Article

作者: Kissman, Elijah N. ; Puerner, Charles ; Barbano, Julia ; Sadowski, Craig ; Bender, Hayden A. ; Pelaez, Jennifer ; Schallies, Karla B. ; Huynh, Roger ; Gibson, Katherine E.

ABSTRACT The cell cycle is a fundamental process involved in bacterial reproduction and cellular differentiation. For Sinorhizobium meliloti , cell cycle outcomes depend on its growth environment. This bacterium shows a tight coupling of DNA replication initiation with cell division during free-living growth. In contrast, it undergoes a novel program of endoreduplication and terminal differentiation during symbiosis within its host. While several DivK regulators at the top of its CtrA pathway have been shown to play an important role in this differentiation process, there is a lack of resolution regarding the downstream molecular activities required and whether they could be unique to the symbiosis cell cycle. The DivK kinase CbrA is a negative regulator of CtrA activity and is required for successful symbiosis. In this work, spontaneous symbiosis suppressors of Δ cbrA were identified as alleles of divL and cckA . In addition to rescuing symbiotic development, they restore wild-type cell cycle progression to free-living Δ cbrA cells. Biochemical characterization of the S. meliloti hybrid histidine kinase CckA in vitro demonstrates that it has both kinase and phosphatase activities. Specifically, CckA on its own has autophosphorylation activity, and phosphatase activity is induced by the second messenger c-di-GMP. Importantly, the CckA A373S suppressor protein of Δ cbrA has a significant loss in kinase activity, and this is predicted to cause decreased CtrA activity in vivo . These findings deepen our understanding of the CbrA regulatory pathway and open new avenues for further molecular characterization of a network pivotal to the free-living cell cycle and symbiotic differentiation of S. meliloti . IMPORTANCESinorhizobium meliloti is a soil bacterium able to form a nitrogen-fixing symbiosis with certain legumes, including the agriculturally important Medicago sativa . It provides ammonia to plants growing in nitrogen-poor soils and is therefore of agricultural and environmental significance as this symbiosis negates the need for industrial fertilizers. Understanding mechanisms governing symbiotic development is essential to either engineer a more effective symbiosis or extend its potential to non-leguminous crops. Here, we identify mutations within cell cycle regulators and find that they control cell cycle outcomes during both symbiosis and free-living growth. As regulators within the CtrA two-component signal transduction pathway, this study deepens our understanding of a regulatory network shaping host colonization, cell cycle differentiation, and symbiosis in an important model organism.

2024-09-01·Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Effects of fasting and environmental factors on appetite regulators in pond loach Misgurnus anguillicaudatus

Article

作者: Lindstrom, Annika ; Volkoff, Helene ; Kuhn, Jannik

The pond loach (Misgurnus anguillicaudatus) is an important aquaculture freshwater species, used as an ornamental fish, food source for humans and angling bait. Pond loaches are resistant to fasting and extreme environmental conditions, including temperature and low oxygen levels. Little is known about how these factors affect the feeding physiology and the endocrine regulation of feeding of loaches. In this study, we examined the effects of fasting, as well as increased temperature and decreased oxygen levels on food intake and transcript levels of appetite regulators. Fasted fish had lower blood glucose levels, and lower expression levels of intestine CCK and PYY, and brain CART1, but had higher levels of brain orexin and ghrelin than fed fish. Fish held at 30 °C had higher food intake, glucose levels, and mRNA levels of intestine CCK and PYY, and brain CART2, but lower brain orexin levels than fish at 20 °C. Fish held at low oxygen levels had a lower food intake, higher intestine CCKa and ghrelin, and brain orexin, CART2 and ghrelin mRNA expression levels than fish held at high O₂ levels. Our results suggest that fasting and high temperatures increase the expression of orexigenic and anorexigenic factors respectively, whereas the increase in expression of both orexigenic and anorexigenic factors in low O₂ environments might not be related to their role in feeding, but possibly to protection from tissue damage. The results of our study might shed new light on how pond loaches are able to cope with extreme environmental conditions such as low food availability, extreme temperatures and hypoxia.