2. Academic Validation
  3. 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

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

  • Int J Mol Sci. 2024 Mar 5;25(5):3008. doi: 10.3390/ijms25053008.
Małgorzata Łupina 1,  Agnieszka Wąsik 2,  Irena Baranowska-Bosiacka 3,  Maciej Tarnowski 4,  Tymoteusz Słowik 5,  Piotr Listos 6,  Jolanta Kotlińska 7,  Danuta Kosik-Bogacka 8,  Izabela Gutowska 9,  Joanna Listos 7
Affiliations

Affiliations

  • 1 Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8b St., 20-090 Lublin, Poland.
  • 2 Department of Neurochemistry, Maj Institute of Pharmacology PAS, Smetna St. 12, 31-343 Kraków, Poland
  • 3 Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111 Szczecin, Poland.
  • 4 Department of Physiology in Health Sciences, Pomeranian Medical University, Żołnierska 54, 70-210 Szczecin, Poland.
  • 5 Experimental Medicine Center, Medical University of Lublin, Jaczewskiego 8d St., 20-090 Lublin, Poland.
  • 6 Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Life Sciences, Głęboka 30, 20-612 Lublin, Poland.
  • 7 Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, Poland.
  • 8 Independent Laboratory of Pharmaceutical Botany, Department of Biology and Medical Parasitology, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
  • 9 Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Broniewskiego 24, 71-460 Szczecin, Poland.
PMID: 38474255 DOI: 10.3390/ijms25053008
Abstract

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.

Keywords

dipeptidyl peptidase-4 inhibitor; dopamine; glucagon-like peptide-1; linagliptin; noradrenaline; serotonin.

Figures
Products