Acute and Chronic Exposure to Linagliptin, a Selective Inhibitor of Dipeptidyl Peptidase-4 (DPP-4), Has an Effect on Dopamine, Serotonin and Noradrenaline Level in the Striatum and Hippocampus of Rats

• Published in: International journal of molecular sciences Vol. 25; no. 5; p. 3008
• Main Authors: Łupina, Małgorzata, Wąsik, Agnieszka, Baranowska-Bosiacka, Irena, Tarnowski, Maciej, Słowik, Tymoteusz, Listos, Piotr, Kotlińska, Jolanta, Kosik-Bogacka, Danuta, Gutowska, Izabela, Listos, Joanna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-03-2024; MDPI
• Subjects: Animals; Brain; Brain research; Cardiac glycosides; Cardiotonic agents; Diabetes; Dipeptidyl Peptidase 4 - metabolism; dipeptidyl peptidase-4 inhibitor; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; Dopamine; Drug dosages; Enzymes; glucagon-like peptide-1; High performance liquid chromatography; Hippocampus - metabolism; Hypoglycemic agents; linagliptin; Linagliptin - pharmacology; Metabolites; Morphine; Neurotransmitter Agents; Noradrenaline; Norepinephrine; Peptides; Phenols; Physiological aspects; Ratios; Rats; RNA; RNA, Messenger; Serotonin; Type 2 diabetes; Poland; dipeptidyl peptidase-4 inhibitor; serotonin; noradrenaline; linagliptin; dopamine; glucagon-like peptide-1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25053008

Linagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that indirectly elevates the glucagon-like peptide-1 (GLP-1) level. The aim of the present study was to check whether linagliptin has an influence on neurotransmission in rat brain. Rats were acutely and chronically exposed to linagliptin (10 and 20 mg/kg, intraperitoneally (i.p.)). Twenty-four hours later, the striatum and hippocampus were selected for further studies. In neurochemical experiments, using high-performance liquid chromatography with electrochemical detection (HPLC-ED), the concentrations of three major neurotransmitters-dopamine, serotonin and noradrenaline-and their metabolites were measured. The analysis of mRNA expression of dopamine (D1 and D2), serotonin (5-HT-1 and 5-HT-2) and noradrenaline (α1 and α2a) receptors was also investigated using real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) in the same brain areas. Linagliptin has the ability to influence the dopaminergic system. In the striatum, the elevation of dopamine and its metabolites was observed after repeated administration of that linagliptin, and in the hippocampus, a reduction in dopamine metabolism was demonstrated. Acute linagliptin exposure increases the serotonin level in both areas, while after chronic linagliptin administration a tendency for the mRNA expression of serotoninergic receptors (5-HT1A and 5-HT2A) to increase was observed. A single instance of exposure to linagliptin significantly modified the noradrenaline level in the striatum and intensified noradrenaline turnover in the hippocampus. The recognition of the interactions in the brain between DPP-4 inhibitors and neurotransmitters and/or receptors is a crucial step for finding novel discoveries in the pharmacology of DPP-4 inhibitors and raises hope for further applications of DPP-4 inhibitors in clinical practices.