Katsouri, Ilektra Petrina and Vandervelpen, Ebert Vinciane G. and Gattor, Albert Owusu and Engelbeen, Sarah and El Sayed, Abdulrahman and Seitaj, Klejdia and Becerra, Eduardo Daniel Morales and Vanderheyden, Patrick M. L. (2022) Complex FFA1 receptor (in)dependent modulation of calcium signaling by free fatty acids. BIOCHEMICAL PHARMACOLOGY, 202: 115150. ISSN 0006-2952, 1873-2968
Full text not available from this repository. (Request a copy)Abstract
The expression of free fatty acid 1 receptors (FFA1R), activated by long chain fatty acids in human pancreatic beta-cells and enhancing glucose-stimulated insulin secretion are an attractive target to treat type 2 diabetes. Yet several clinical studies with synthetic FFA1R agonists had to be discontinued due to cytotoxicity and/or so-called "liver concerns". It is not clear whether these obstructions are FFA1R dependent. In this context we used CHO-AEQ cells expressing the bioluminescent calcium-sensitive protein aequorin to investigate calcium signaling elicited by FFA1 receptor ligands alpha-linolenic acid (ALA), oleic acid (OLA) and myristic acid (MYA). This study revealed complex modulation of intracellular calcium signaling by these fatty acids. First these compounds elicited a typical transient increase of intracellular calcium via binding to FFA1 receptors. Secondly slightly higher concentrations of ALA substantially reduced ATP mediated calcium responses in CHO-AEQ cells and Angiotensin II responses in CHO-AEQ cells expressing human AT 1 receptors. This effect was less pronounced with MYA and OLA and was not linked to FFA1 receptor activation nor to acute cytotoxicity as a result of plasma membrane perturbation. Yet it can be hypothesized that, in line with previous studies, unsaturated long chain fatty acids such as ALA and OLA are capable of inactivating the G-proteins involved in purinergic and Angiotensin AT(1) receptor calcium signaling. Alternatively the ability of fatty acids to deplete intracellular calcium stores might underly the observed cross-inhibition of these receptor responses in the same cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-COUPLED RECEPTORS; PANCREATIC BETA-CELL; OLEIC-ACID; INTRACELLULAR CALCIUM; INSULIN-SECRETION; DIABETES-MELLITUS; GPR40 AGONISTS; KINASE-C; RISK; BINDING; Free fatty acid 1 receptor; FFA1R ligands; ATP; Angiotensin II; Calcium signaling |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 05:56 |
| Last Modified: | 30 Jan 2024 05:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58043 |
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