Last update 01 Nov 2024

CCKA

Last update 01 Nov 2024

Basic Info

Synonyms

CCK-A receptor, CCK-AR, CCK1-R

+ [6]

Introduction

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.

Drugs associated with CCKA

Sincalide

Target

CCKA x CCKB

Mechanism

CCKA agonists [+1]

Active Org.

Maia Pharmaceuticals, Inc. [+1]

Originator Org.

Bracco International BV

Active Indication

Gallbladder Diseases [+3]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date21 Jul 1976

PNB-001

Target

CCKA x CCKB

Mechanism

CCKA antagonists [+1]

Active Org.

PNB Vesper Life Sciences Pvt. Ltd

Originator Org.

PNB Vesper Life Sciences Pvt. Ltd

Active Indication

COVID-19 [+2]

Inactive Indication-

Drug Highest PhasePhase 3

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Dexloxiglumide

Target

CCKA

Mechanism

CCKA antagonists

Active Org.

Allergan Ltd. (Ireland)

Originator Org.

Rottapharm SpA

Active Indication

Irritable Bowel Syndrome

Inactive Indication

Dyspepsia [+2]

Drug Highest PhasePhase 3

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with CCKA

CTRI/2022/10/046658 / RecruitingPhase 2

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

Start Date28 Oct 2022

Sponsor / Collaborator

PNB Vesper Life Sciences Pvt. Ltd

[+1]

CTRI/2021/09/036411 / RecruitingPhase 3

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

Start Date27 Sep 2021

Sponsor / Collaborator

PNB Vesper Life Sciences Pvt. Ltd

CTRI/2020/10/028423 / CompletedPhase 2

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

Start Date28 Oct 2020

Sponsor / Collaborator

PNB Vesper Life Sciences Pvt. Ltd

[+1]

100 Clinical Results associated with CCKA

100 Translational Medicine associated with CCKA

0 Patents (Medical) associated with CCKA

1,080

Literatures (Medical) associated with CCKA

01 Nov 2024·Neurology Neuroimmunology & Neuroinflammation

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

Article

Author: 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.

24 Oct 2024·Journal of Bacteriology

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

Article

Author: 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.

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

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

Article

Author: 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.

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