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http://dx.doi.org/10.4142/jvs.21188

Xylazole inhibits NO-cGMP pathway in fetal rat nerve cells  

Wang, Xinyu (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Wu, Yue (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Liu, Lin (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Bai, Hui (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Zhang, Zhiheng (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Zhao, Mingchao (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Ma, Tianwen (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Song, Xiaopeng (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Jia, Lina (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Lv, Liangyu (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Yu, Yue (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Xu, Xinyu (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Chen, Hong (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Gao, Li (Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University)
Publication Information
Journal of Veterinary Science / v.23, no.1, 2022 , pp. 16.1-16.13 More about this Journal
Abstract
Background: Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown. Objectives: This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl. Methods: Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 ㎍/ mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated. Results: Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro. Conclusions: This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway.
Keywords
Xylazole; anesthesia; cyclic GMP; gamma-aminobutyric acid; glutamic acid;
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1 Rosenberg PA, Aizenman E. Hundred-fold increase in neuronal vulnerability to glutamate toxicity in astrocyte-poor cultures of rat cerebral cortex. Neurosci Lett. 1989;103(2):162-168.   DOI
2 Yan N, Chen N, Lu J, Wang Y, Wang W. Electroacupuncture at acupoints could predict the outcome of anterior nucleus thalamus high-frequency electrical stimulation in medically refractory epilepsy. Med Hypotheses. 2013;81(3):426-428.   DOI
3 Dachsel JC, Behrouz B, Yue M, Beevers JE, Melrose HL, Farrer MJ. A comparative study of Lrrk2 function in primary neuronal cultures. Parkinsonism Relat Disord. 2010;16(10):650-655.   DOI
4 Schmitt H, Le Douarec JC, Petillot N. Antagonism of the antinociceptive action of xylazine, an alpha-sympathomimetic agent, by adrenoceptor and cholinoceptor blocking agents. Neuropharmacology. 1974;13(5):295-303.   DOI
5 Changmin H, Jianguo C, Dongming L, Guohong L, Mingxing D. Effects of xylazole alone and in combination with ketamine on the metabolic and neurohumoral responses in healthy dogs. Vet Anaesth Analg. 2010;37(4):322-328.   DOI
6 Tsurugizawa T, Uematsu A, Uneyama H, Torii K. Effects of isoflurane and alpha-chloralose anesthesia on BOLD fMRI responses to ingested L-glutamate in rats. Neuroscience. 2010;165(1):244-251.   DOI
7 Janicki PK, Horn JL, Singh G, Franks WT, Janson VE, Franks JJ. Increased anesthetic requirements for isoflurane, halothane, enflurane and desflurane in obese Zucker rats are associated with insulin-induced stimulation of plasma membrane Ca(2+)-ATPase. Life Sci. 1996;59(17):PL269-PL275.   DOI
8 Li KC, Zhang FX, Li CL, Wang F, Yu MY, Zhong YQ, et al. Follistatin-like 1 suppresses sensory afferent transmission by activating Na+,K+-ATPase. Neuron. 2011;69(5):974-987.   DOI
9 Shen K, Johnson DW, Gobe GC. The role of cGMP and its signaling pathways in kidney disease. Am J Physiol Renal Physiol. 2016;311(4):F671-F681.   DOI
10 van Staveren WC, Steinbusch HW, Markerink-van Ittersum M, Behrends S, de Vente J. Species differences in the localization of cGMP-producing and NO-responsive elements in the mouse and rat hippocampus using cGMP immunocytochemistry. Eur J Neurosci. 2004;19(8):2155-2168.   DOI
11 Tao R, Hjorth S. Alpha 2-adrenoceptor modulation of rat ventral hippocampal 5-hydroxytryptamine release in vivo. Naunyn Schmiedebergs Arch Pharmacol. 1992;345(2):137-143.   DOI
12 Rong YF, Hsu WH, Hembrough FB. Effects of xylazole on heart rate and blood pressure in conscious dogs. Zhongguo Yao Li Xue Bao. 1989;10(5):410-414.
13 Hsu WH, Rong YF, Hembrough FB. The effects of jingsongling, a xylazine analog, on mean arterial blood pressure and heart rate in dogs--influences of yohimbine, tolazoline, prazosin, and atropine. J Vet Pharmacol Ther. 1989;12(3):283-288.   DOI
14 Xiong HJ. Veterinary Anaesthesia. Beijing: China Agricultural Press; 2004.
15 Song J, Sun T, Tang Z, Ruan Y, Liu K, Rao K, et al. Exosomes derived from smooth muscle cells ameliorate diabetes-induced erectile dysfunction by inhibiting fibrosis and modulating the NO/cGMP pathway. J Cell Mol Med. 2020;24(22):13289-13302.   DOI
16 Giles TD. Aspects of nitric oxide in health and disease: a focus on hypertension and cardiovascular disease. J Clin Hypertens (Greenwich). 2006;8(12 Suppl 4):2-16.
17 Sharma HS. Interaction between amino acid neurotransmitters and opioid receptors in hyperthermia-induced brain pathology. Prog Brain Res. 2007;162:295-317.   DOI
18 Ding Y, Yao P, Hong T, Han Z, Zhao B, Chen W. The NO-cGMP-PKG signal transduction pathway is involved in the analgesic effect of early hyperbaric oxygen treatment of neuropathic pain. J Headache Pain. 2017;18(1):51.   DOI
19 Hammond C. Cellular and Molecular Neurobiology. New York: Academic Press; 1996.
20 Pin JP, Duvoisin R. The metabotropic glutamate receptors: structure and functions. Neuropharmacology. 1995;34(1):1-26.   DOI
21 Windels F, Kiyatkin EA. General anesthesia as a factor affecting impulse activity and neuronal responses to putative neurotransmitters. Brain Res. 2006;1086(1):104-116.   DOI
22 Beaudoin GM 3rd, Lee SH, Singh D, Yuan Y, Ng YG, Reichardt LF, et al. Culturing pyramidal neurons from the early postnatal mouse hippocampus and cortex. Nat Protoc. 2012;7(9):1741-1754.   DOI
23 Andoh T, Chock PB, Chiueh CC. Preconditioning-mediated neuroprotection: role of nitric oxide, cGMP, and new protein expression. Ann N Y Acad Sci. 2002;962(1):1-7.   DOI
24 Legrand MC, Benessiano J, Levy BI. Endothelium, mechanical compliance, and cGMP content in the carotid artery from spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1993;21(1 Suppl 1):S26-S30.   DOI
25 Choi DW, Koh JY, Peters S. Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J Neurosci. 1988;8(1):185-196.   DOI
26 Wang Y, Jia B, Li X, Guo C, Li L, Li Y, et al. The effect of xylazine anesthesia on goats central NO/cGMP pathway. Pak Vet J. 2017;37:415-420.
27 Lacza Z, Horn TF, Snipes JA, Zhang J, Roychowdhury S, Horvath EM, et al. Lack of mitochondrial nitric oxide production in the mouse brain. J Neurochem. 2004;90(4):942-951.   DOI
28 Quinn AC, Petros AJ, Vallance P. Nitric oxide: an endogenous gas. Br J Anaesth. 1995;74(4):443-451.   DOI
29 Karacay B, Bonthius DJ. The neuronal nitric oxide synthase (nNOS) gene and neuroprotection against alcohol toxicity. Cell Mol Neurobiol. 2015;35(4):449-461.   DOI
30 Sagi Y, Heiman M, Peterson JD, Musatov S, Scarduzio M, Logan SM, et al. Nitric oxide regulates synaptic transmission between spiny projection neurons. Proc Natl Acad Sci U S A. 2014;111(49):17636-17641.   DOI
31 Buchanan RJ, Gjini K, Darrow D, Varga G, Robinson JL, Nadasdy Z. Glutamate and GABA concentration changes in the globus pallidus internus of Parkinson's patients during performance of implicit and declarative memory tasks: a report of two subjects. Neurosci Lett. 2015;589:73-78.   DOI
32 Meberg PJ, Miller MW. Culturing hippocampal and cortical neurons. Methods Cell Biol. 2003;71:111-127.   DOI
33 Vulliemoz Y, Shen H, Virag L. Alpha-2 adrenoceptor agonists decrease cyclic guanosine 3',5'-monophosphate in the mouse brain. Anesthesiology. 1996;85(3):544-550.   DOI
34 Manev H, Favaron M, Guidotti A, Costa E. Delayed increase of Ca2+ influx elicited by glutamate: role in neuronal death. Mol Pharmacol. 1989;36(1):106-112.
35 Neitz A, Mergia E, Imbrosci B, Petrasch-Parwez E, Eysel UT, Koesling D, et al. Postsynaptic NO/cGMP increases NMDA receptor currents via hyperpolarization-activated cyclic nucleotide-gated channels in the hippocampus. Cereb Cortex. 2014;24(7):1923-1936.   DOI
36 Bahar M, Berman S, Chanimov M, Weissgarten J, Averbukh Z, Cohen ML, et al. Intrathecal anaesthesia alters intracellular Ca2+/Mg2+ homeostasis in the spinal cord neurones of experimental rats. Eur J Anaesthesiol. 2001;18(4):231-237.   DOI