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
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 linag...
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2024-03-01
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| author | Małgorzata Łupina Agnieszka Wąsik Irena Baranowska-Bosiacka Maciej Tarnowski Tymoteusz Słowik Piotr Listos Jolanta Kotlińska Danuta Kosik-Bogacka Izabela Gutowska Joanna Listos |
| author_facet | Małgorzata Łupina Agnieszka Wąsik Irena Baranowska-Bosiacka Maciej Tarnowski Tymoteusz Słowik Piotr Listos Jolanta Kotlińska Danuta Kosik-Bogacka Izabela Gutowska Joanna Listos |
| author_sort | Małgorzata Łupina |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-25T00:28:17Z |
| format | Article |
| id | doaj.art-dd983bbf8e3243e78f4944e070a2434b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-25T00:28:17Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dd983bbf8e3243e78f4944e070a2434b2024-03-12T16:47:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01255300810.3390/ijms25053008Acute 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 RatsMałgorzata Łupina0Agnieszka Wąsik1Irena Baranowska-Bosiacka2Maciej Tarnowski3Tymoteusz Słowik4Piotr Listos5Jolanta Kotlińska6Danuta Kosik-Bogacka7Izabela Gutowska8Joanna Listos9Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8b St., 20-090 Lublin, PolandDepartment of Neurochemistry, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, PolandDepartment of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111 Szczecin, PolandDepartment of Physiology in Health Sciences, Pomeranian Medical University, Żołnierska 54, 70-210 Szczecin, PolandExperimental Medicine Center, Medical University of Lublin, Jaczewskiego 8d St., 20-090 Lublin, PolandDepartment of Pathological Anatomy, Faculty of Veterinary Medicine, University of Life Sciences, Głęboka 30, 20-612 Lublin, PolandDepartment of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, PolandIndependent Laboratory of Pharmaceutical Botany, Department of Biology and Medical Parasitology, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, PolandDepartment of Biochemistry and Human Nutrition, Pomeranian Medical University, Broniewskiego 24, 71-460 Szczecin, PolandDepartment of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, PolandLinagliptin 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.https://www.mdpi.com/1422-0067/25/5/3008linagliptinglucagon-like peptide-1dipeptidyl peptidase-4 inhibitordopamineserotoninnoradrenaline |
| spellingShingle | Małgorzata Łupina Agnieszka Wąsik Irena Baranowska-Bosiacka Maciej Tarnowski Tymoteusz Słowik Piotr Listos Jolanta Kotlińska Danuta Kosik-Bogacka Izabela Gutowska Joanna Listos 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 International Journal of Molecular Sciences linagliptin glucagon-like peptide-1 dipeptidyl peptidase-4 inhibitor dopamine serotonin noradrenaline |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | linagliptin glucagon-like peptide-1 dipeptidyl peptidase-4 inhibitor dopamine serotonin noradrenaline |
| url | https://www.mdpi.com/1422-0067/25/5/3008 |
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