MKC-231, a choline uptake enhancer: (3) Mode of action of MKC-231 in the enhancement of high-affinity choline uptake.

J Neural Transm (Vienna)

Pharmacology Department IV, Pharmacology Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.

Published: July 2008

MKC-231, a putative cholinergic activity, is reported to improve learning and memory impaired in AF64A-treated animals. MKC-231 enhances high-affinity choline uptake (HACU) known as the rate-limiting step of acetylcholine (ACh) synthesis. We investigated the mode of action (MOA) of HACU enhancement by MKC-231. Intracerebroventricular (i.c.v.) injections of AF64A (3 nmol/brain) resulted in significant HACU reduction in hippocampal synaptosomes. Treatment with MKC-231 increased Vmax of HACU and Bmax of [3H]-HC-3 binding 1.6 and 1.7-fold, respectively. In studies of [3H]-MKC-231 binding and Biacore analysis, MKC-231 showed noticeable affinity for cloned high-affinity choline transporters (CHT1). The present study suggests that MKC-231 directly affects trafficking of CHT1 and increases the numbers of transporter, working for HACU, at the synaptic membrane.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00702-008-0049-0DOI Listing

Publication Analysis

Top Keywords

choline uptake
12
high-affinity choline
12
mkc-231
8
mode action
8
hacu
5
mkc-231 choline
4
uptake enhancer
4
enhancer mode
4
action mkc-231
4
mkc-231 enhancement
4

Similar Publications

Fatty liver impairs liver function and reduces productivity in dairy cows. Our previous in vivo findings demonstrated that branched-chain amino acids (BCAA) or branched-chain ketoacid (BCKA) improved liver function and lactation performance in dairy cows; however, the underlying mechanisms remain unclear. This study aimed to assess the impact of BCAA or BCKA supplementation on intracellular triglyceride (TG) accumulation, lipid metabolism, antioxidant response, and apoptosis in hepatocytes.

View Article and Find Full Text PDF

Maternal plasma choline levels are positively correlated with maternal and placental phospholipid-DHA content in females with obesity who receive DHA supplementation.

J Nutr

December 2024

Division of Reproductive Sciences, Department of Obstetrics & Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Section of Neonatology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address:

Pregnancies complicated by maternal obesity are characterized by metabolic differences affecting placental nutrient transport and fetal development. Docosahexaenoic acid (DHA) is critical for fetal brain development and is primarily incorporated into phosphatidylcholine (PC). Recent evidence suggests choline may enhance PC-DHA synthesis; however, data on the impact of maternal plasma choline on placental phospholipid DHA content in females with obesity are limited.

View Article and Find Full Text PDF

Detachable Cyclic Poly(ethylene glycol)-Embedded Choline Phosphate Liposome Used for Long-Acting and Accurate Cancer Chemo-Immunotherapy with High Security.

ACS Appl Mater Interfaces

January 2025

Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, School of Chemistry, Northeast Normal University, Changchun 130024, China.

Liposomes have attracted attention in biomedicine and pharmacy for their benefits including reduced toxicity, extended pharmacokinetics, and biocompatibility. However, their limitations include susceptibility to blood clearance, rapid disintegration, and lack of functionality, restricting their further applications. To address these challenges, inspired by the unique topological features of cyclic polymers and the specific binding property of the choline phosphate (CP) lipid, dipole-dipole interactions between CP molecules are utilized to create a detachable cyclic PEG-embedded CP liposome (d-cycPEG-lipo).

View Article and Find Full Text PDF

Development of smart films based on soy protein and cow horn dissolved in a deep eutectic solvent: Physicochemical and environmental assessment.

Int J Biol Macromol

December 2024

BIOMAT Research Group, University of the Basque Country (UPV/EHU), Escuela de Ingeniería de Gipuzkoa, Europa Plaza 1, 20018 Donostia-San Sebastián, Spain; BCMaterials, Basque Center for Materials, Applications and Nanostructures, UPV/EHU Science Park, 48940 Leioa, Spain; Proteinmat Materials SL, Avenida de Tolosa 72, 20018 Donostia-San Sebastián, Spain. Electronic address:

With the urge to reduce the use of petroleum-based materials, the aim of this work is to valorize biowaste to develop smart films through a sustainable fabrication way. In this regard, choline chloride/urea (1:2) deep eutectic solvent (DES) at different concentrations (25, 40, 50 and 75 wt%) was used to dissolve cow horn, used as reinforcement agent in soy protein films. The film fabrication was carried out by compression molding, a fast and cost-effective.

View Article and Find Full Text PDF

Hepatocyte hopping is the hepatocyte-to-sinusoid-to-hepatocyte shuttling that increases the efficiency of hepatic elimination of xenobiotics. This phenomenon is mediated efflux of hepatic metabolites by Mrp3 and reuptake by Oatp transporters in sequential hepatocytes until eventual biliary efflux by Mrp2. Sorafenib-glucuronide (SFB-G), the major metabolite of sorafenib (SFB), undergoes hepatocyte hopping, leading to efficient biliary elimination.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!