The cardiovascular effects of a chimeric opioid peptide based on morphiceptin and PFRTic-NH2 |
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| Affiliation: | 1. Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, China;2. The Core Laboratory of the First Affiliated Hospital, Lanzhou University, 1 Donggang West Road, Lanzhou 730000, China;3. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, China;1. Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education, School of Energy and Power Engineering, Xi''an Jiaotong University, Xi''an, Shaanxi 710049, China;2. Department of Mechanical and Aerospace Engineering, University of Missouri, Columbia, MO 65211, USA;1. MOE Key Laboratory of Bioinformatics, Cell Biology and Development Center, School of Life Sciences, Tsinghua University, Beijing 100084, China;2. Peking University Research Center on Aging, Beijing 100191, China;3. Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China;1. Division of Medical Oncology, Washington University School of Medicine, St Louis, MO, USA;2. Biostatistics Shared Resource, Washington University School of Medicine, St Louis, MO, USA;3. Alvin J Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA;4. Division of Oncology, University of Kansas School of Medicine, Kansas City, KS, USA;5. Department of Medicine, University of Michigan, Ann Arbor, MI, USA;6. University of California San Diego Moores Cancer Center, La Jolla, CA, USA;7. Department of Medicine, St Louis University, St Louis, MO, USA;8. Department of Medicine, Division of Hematology-Oncology, and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA;9. Department of Medicine, Wilmont Cancer Institute at the University of Rochester, Rochester, NY, USA;10. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt;11. Department of Pharmaceutical and Administrative Sciences, St Louis College of Pharmacy, St Louis, MO, USA;12. Winship Cancer Institute of Emory University, Atlanta, GA, USA;1. Anesthesiology Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;2. Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;3. Department of Psychiatry, UMKC School of Medicine, 1000 E. 24th Street, Kansas City, MO, 64108, United States;4. Department of Psychiatry and Behavioral Science, UT Health McGovern Medical School, Houston, TX, 77054, United States;5. Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;1. Institute of Biochemistry, Biological Research Centre, Temesvári krt. 62., H-6726 Szeged, Hungary;2. Doctoral School of Theoretical Medicine, Faculty of Medicine, University of Szeged, Dóm tér 10., H-6720 Szeged, Hungary;3. Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary;4. Department of Physiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, Dóm tér 10., Hungary |
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| Abstract: | MCRT (YPFPFRTic-NH2) is a chimeric opioid peptide based on morphiceptin and PFRTic-NH2. In order to assess the cardiovascular effect of MCRT, it was administered by intravenous (i.v.) injection targeting at the peripheral nervous system and by intracerebroventricular (i.c.v.) injection targeting at the central nervous system. Naloxone and l-NAME were injected before MCRT to investigate possible interactions with MCRT. Results show that administration of MCRT by i.v. or i.c.v. injection could induce bradycardia and decrease in mean arterial pressure (MAP) at a greater degree than that with morphiceptin and PFRTic-NH2. When MCRT and NPFF were coinjected, we observed a dose-dependent weakening of these cardiovascular effects by MCRT. Because naloxone completely abolished the cardiovascular effects of MCRT, we conclude that opioid receptors are involved in regulating the MAP of MCRT regardless of modes of injection. The effect of MCRT on heart rate is completely dependent on opioid receptors when MCRT was administered by i.c.v. instead of i.v. The central nitric oxide (NO) pathway is involved in regulating blood pressure by MCRT under both modes of injection, but the peripheral NO pathway had no effect on lowering blood pressure mediated by MCRT when it was administered by i.c.v. Based on the results from different modes of injection, the regulation of heart rate by MCRT mainly involves in the central NO pathway. Lastly, we observed that the cardiovascular effects of MCRT such as bradycardia and decrease of blood pressure, were stronger than that of its parent peptides. Opioid receptors and the NO pathway are involved in the cardiovascular regulation by MCRT, and their degree of involvement differs between intravenous and intracerebroventricular injection. |
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