Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

Irisin Relaxes Rat Trachea via KV Channels, KATP Channels, and BKCa Channels

Author(s): Sadettin Demirel* and Fadil Ozyener

Volume 29, Issue 9, 2022

Published on: 03 September, 2022

Page: [760 - 768] Pages: 9

DOI: 10.2174/0929866529666220729115541

Price: $65

Abstract

Background: This study aimed to investigate the effects of irisin on rat tracheal smooth muscle contraction-relaxation responses and the roles of voltage-gated potassium (KV) channels, ATP-sensitive potassium (KATP) channels, and large-conductance calcium-activated potassium (BKCa) channels in these effects.

Methods: Isometric contraction and relaxation responses of tracheal segments were measured using the tissue bath method. Submaximal contractions were induced by ACh (10-5 M) or KCl (60 mM), and then concentration-response curves of irisin (10-9 to 10-6 M) were obtained. For the temporal control, a double-distilled water group was formed. ACh and irisin were added to the baths after tracheal segments were incubated with 4-AP (KV channel blocker), glibenclamide (KATP channel blocker), TEA, and iberiotoxin (BKCa channel blockers) to assess the role of K+ channels. In addition, a vehicle group was performed for the solvent dimethyl sulfoxide (DMSO).

Results: Irisin exhibited the relaxant effects in tracheal segments precontracted with both ACh and KCl at concentrations of 10-8-10-6 M (p<0.05). Besides, incubations of 4-AP, glibenclamide, TEA, and iberiotoxin significantly inhibited the irisin-mediated relaxation (p<0.05), whereas DMSO incubation did not modulate irisin responses (p>0.05).

Conclusion: In conclusion, the first physiological results on the relaxant effects of irisin in rat trachea were obtained. Our findings demonstrated that irisin mediates concentration-dependent relaxation in rat tracheas. Moreover, the present study reported for the first time that irisin-induced bronchorelaxation is associated with the activity of the K+ channels.

Keywords: Irisin, trachea, bronchodilation, KV channels, KATP channels, BKCa channels.

Graphical Abstract

[1]
Boström, P.; Wu, J.; Jedrychowski, M.P.; Korde, A.; Ye, L.; Lo, J.C.; Rasbach, K.A.; Boström, E.A.; Choi, J.H.; Long, J.Z.; Kajimura, S.; Zingaretti, M.C.; Vind, B.F.; Tu, H.; Cinti, S.; Højlund, K.; Gygi, S.P.; Spiegelman, B.M.A. PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 2012, 481(7382), 463-468.
[http://dx.doi.org/10.1038/nature10777] [PMID: 22237023]
[2]
Kelly, D.P. Medicine. Irisin, light my fire. Science, 2012, 336(6077), 42-43.
[http://dx.doi.org/10.1126/science.1221688] [PMID: 22491843]
[3]
Sanchis-Gomar, F.; Lippi, G.; Mayero, S.; Perez-Quilis, C.; García-Giménez, J.L. Irisin: A new potential hormonal target for the treatment of obesity and type 2 diabetes. J. Diabetes, 2012, 4(3), 196.
[http://dx.doi.org/10.1111/j.1753-0407.2012.00194.x] [PMID: 22372821]
[4]
Villarroya, F. Irisin, turning up the heat. Cell Metab., 2012, 15(3), 277-278.
[http://dx.doi.org/10.1016/j.cmet.2012.02.010] [PMID: 22405065]
[5]
Kubo, H.; Asai, K.; Kojima, K.; Sugitani, A.; Kyomoto, Y.; Okamoto, A.; Yamada, K.; Ijiri, N.; Watanabe, T.; Hirata, K.; Kawaguchi, T. Exercise ameliorates emphysema of cigarette smoke-induced COPD in mice through the exercise-irisin-Nrf2 axis. Int. J. Chron. Obstruct. Pulmon. Dis., 2019, 14, 2507-2516.
[http://dx.doi.org/10.2147/COPD.S226623] [PMID: 31814716]
[6]
Ijiri, N.; Kanazawa, H.; Asai, K.; Watanabe, T.; Hirata, K. Irisin, a newly discovered myokine, is a novel biomarker associated with physical activity in patients with chronic obstructive pulmonary disease. Respirology, 2015, 20(4), 612-617.
[http://dx.doi.org/10.1111/resp.12513] [PMID: 25800067]
[7]
Sugiyama, Y.; Asai, K.; Yamada, K.; Kureya, Y.; Ijiri, N.; Watanabe, T.; Kanazawa, H.; Hirata, K. Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis., 2017, 12, 765-772.
[http://dx.doi.org/10.2147/COPD.S126233] [PMID: 28424548]
[8]
Papp, C.; Pak, K.; Erdei, T.; Juhasz, B.; Seres, I.; Szentpéteri, A.; Kardos, L.; Szilasi, M.; Gesztelyi, R.; Zsuga, J. Alteration of the irisin-brain-derived neurotrophic factor axis contributes to disturbance of mood in COPD patients. Int. J. Chron. Obstruct. Pulmon. Dis., 2017, 12, 2023-2033.
[http://dx.doi.org/10.2147/COPD.S135701] [PMID: 28744117]
[9]
Szilasi, M.E.; Pak, K.; Kardos, L.; Varga, V.E.; Seres, I.; Mikaczo, A.; Fodor, A.; Szilasi, M.; Tajti, G.; Papp, C.; Gesztelyi, R.; Zsuga, J. The alteration of irisin-brain-derived neurotrophic factor axis parallels severity of distress disorder in bronchial asthma patients. Front. Neurosci., 2017, 11, 653.
[http://dx.doi.org/10.3389/fnins.2017.00653] [PMID: 29217995]
[10]
Zhang, L.; Sun, Y. Muscle-bone crosstalk in chronic obstructive pulmonary disease. Front. Endocrinol., 2021, 12, 724911.
[http://dx.doi.org/10.3389/fendo.2021.724911] [PMID: 34650518]
[11]
Mitzner, W. Airway smooth muscle: The appendix of the lung. Am. J. Respir. Crit. Care Med., 2004, 169(7), 787-790.
[http://dx.doi.org/10.1164/rccm.200312-1636PP] [PMID: 14742304]
[12]
Knox, A.J.; Tattersfield, A.E. Airway smooth muscle relaxation. Thorax, 1995, 50(8), 894-901.
[http://dx.doi.org/10.1136/thx.50.8.894] [PMID: 7570444]
[13]
Pereira-de-Morais, L.; Silva, A.A.; da Silva, R.E.R.; Ferraz Navarro, D.M.D.A.; Melo Coutinho, H.D.; Menezes, I.R.A.; Kerntopf, M.R.; Cunha, F.A.B.D.; Leal-Cardoso, J.H.; Barbosa, R. Myorelaxant action of the Dysphania ambrosioides (L.) Mosyakin & Clemants essential oil and its major constituent α-terpinene in isolated rat trachea. Food Chem., 2020, 325, 126923.
[http://dx.doi.org/10.1016/j.foodchem.2020.126923] [PMID: 32387952]
[14]
Byun, K.; Lee, S. The potential role of irisin in vascular function and atherosclerosis: A review. Int. J. Mol. Sci., 2020, 21(19), 7184.
[http://dx.doi.org/10.3390/ijms21197184] [PMID: 33003348]
[15]
Jespersen, B.; Tykocki, N.R.; Watts, S.W.; Cobbett, P.J. Measurement of smooth muscle function in the isolated tissue bath-applications to pharmacology research. J. Vis. Exp., 2015, 52324(95), 52324.
[http://dx.doi.org/10.3791/52324] [PMID: 25650585]
[16]
Dogan, M.F.; Yildiz, O.; Arslan, S.O.; Ulusoy, K.G. Potassium channels in vascular smooth muscle: A pathophysiological and pharmacological perspective. Fundam. Clin. Pharmacol., 2019, 33(5), 504-523.
[http://dx.doi.org/10.1111/fcp.12461] [PMID: 30851197]
[17]
Sahin, Y.; Yildirim, E.; Yurdakok Dikmen, B. Effects of Gamithromycin and Tulathromycin on bovine tracheal smooth muscle. Etlik Vet. Mikrobiyol. Derg., 2020, 31, 140-146.
[http://dx.doi.org/10.35864/evmd.762503]
[18]
Beeh, K.M. The role of bronchodilators in preventing exacerbations of chronic obstructive pulmonary disease. Tuberc. Respir. Dis., 2016, 79(4), 241-247.
[http://dx.doi.org/10.4046/trd.2016.79.4.241] [PMID: 27790275]
[19]
Pedersen, B.K.; Febbraio, M.A. Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nat. Rev. Endocrinol., 2012, 8(8), 457-465.
[http://dx.doi.org/10.1038/nrendo.2012.49] [PMID: 22473333]
[20]
Demirel, S.; Sahinturk, S.; Isbil, N.; Ozyener, F. Physiological role of K+ channels in irisin-induced vasodilation in rat thoracic aorta. Peptides, 2022, 147, 170685.
[http://dx.doi.org/10.1016/j.peptides.2021.170685] [PMID: 34748790]
[21]
Undale, V.R.; Jagtap, P.N.; Yadav, A.V.; Sangamnerkar, S.K.; Upasani, C.D.; Bhosale, A.V. An isolated chicken ileum: Alternative to laboratory animals for isolated tissue experimentation. IOSR J. Pharm., 2012, 2(5), 39-45.
[http://dx.doi.org/10.9790/3013-25203945]
[22]
Abdur Rahman, H.M.; Rasool, M.F.; Imran, I. Pharmacological studies pertaining to smooth muscle relaxant, platelet aggregation inhibitory and hypotensive effects of Ailanthus altissima. Evid. Based Complement. Alternat. Med., 2019, 7, 1-14.
[http://dx.doi.org/10.1155/2019/1871696]
[23]
Sahinturk, S.; Demirel, S.; Ozyener, F.; Isbil, N. [Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels. Gen. Physiol. Biophys., 2021, 40(5), 427-434.
[http://dx.doi.org/10.4149/gpb_2021028] [PMID: 34602456]
[24]
Demirel, S. Şahintürk, S.; Işbil, N.; Özyener, F. Irisin relaxes rat thoracic aorta through activating signaling pathways implicating protein kinase C. Turk. J. Med. Sci.,, 2021.
[http://dx.doi.org/10.3906/sag-2105-113] [PMID: 34773690]
[25]
Erdem, A.O.; Erel, V.K.; Girit, Ö. Erdoğan, H.; Özkısacık, S.; Yazıcı, M. Effects of local anesthetics on smooth muscle tissue in rat trachea: An in vitro study. Turk. Thorac. J., 2020, 21(4), 223-227.
[http://dx.doi.org/10.5152/TurkThoracJ.2019.19016] [PMID: 32687781]
[26]
Wang, H.W.; Liu, S.C.; Chao, P.Z.; Lee, F.P. Menthol inhibiting parasympathetic function of tracheal smooth muscle. Int. J. Med. Sci., 2016, 13(12), 923-928.
[http://dx.doi.org/10.7150/ijms.17042] [PMID: 27994497]
[27]
Boskabady, M.H.; Kiani, S.; Rakhshandah, H. Relaxant effects of Rosa damascena on guinea pig tracheal chains and its possible mechanism(s). J. Ethnopharmacol., 2006, 106(3), 377-382.
[http://dx.doi.org/10.1016/j.jep.2006.01.013] [PMID: 16504433]
[28]
Säfholm, J.; Abma, W.; Liu, J.; Balgoma, D.; Fauland, A.; Kolmert, J.; Wheelock, C.E.; Adner, M.; Dahlén, S.E. Prostaglandin D2 inhibits mediator release and antigen induced bronchoconstriction in the Guinea pig trachea by activation of DP1 receptors. Eur. J. Pharmacol., 2021, 907, 174282.
[http://dx.doi.org/10.1016/j.ejphar.2021.174282] [PMID: 34175307]
[29]
Fu, J.; Han, Y.; Wang, J.; Liu, Y.; Zheng, S.; Zhou, L.; Jose, P.A.; Zeng, C. Irisin lowers blood pressure by improvement of endothelial dysfunction via AMPK-Akt-eNOS-NO pathway in the spontaneously hypertensive rat. J. Am. Heart Assoc., 2016, 5(11), e003433.
[http://dx.doi.org/10.1161/JAHA.116.003433] [PMID: 27912206]
[30]
Menezes, P.M.N.; Brito, M.C.; de Paiva, G.O.; Dos Santos, C.O.; de Oliveira, L.M.; de Araújo Ribeiro, L.A.; de Lima, J.T.; Lucchese, A.M.; Silva, F.S. Relaxant effect of Lippia origanoides essential oil in guinea-pig trachea smooth muscle involves potassium channels and soluble guanylyl cyclase. J. Ethnopharmacol., 2018, 220, 16-25.
[http://dx.doi.org/10.1016/j.jep.2018.03.040] [PMID: 29609011]
[31]
Memarzia, A.; Amin, F.; Saadat, S.; Jalali, M.; Ghasemi, Z.; Boskabady, M.H. The contribution of beta-2 adrenergic, muscarinic and histamine (H1) receptors, calcium and potassium channels and cyclooxygenase pathway in the relaxant effect of Allium cepa L. on the tracheal smooth muscle. J. Ethnopharmacol., 2019, 241, 112012.
[http://dx.doi.org/10.1016/j.jep.2019.112012] [PMID: 31170518]
[32]
de Wit, C.; Wölfle, S.E. EDHF and gap junctions: Important regulators of vascular tone within the microcirculation. Curr. Pharm. Biotechnol., 2007, 8(1), 11-25.
[http://dx.doi.org/10.2174/138920107779941462] [PMID: 17311549]
[33]
Clark, S.G.; Fuchs, L.C. Role of nitric oxide and Ca++-dependent K+ channels in mediating heterogeneous microvascular responses to acetylcholine in different vascular beds. J. Pharmacol. Exp. Ther., 1997, 282(3), 1473-1479.
[PMID: 9316861]
[34]
Mulvany, M.J.; Aalkjaer, C. Structure and function of small arteries. Physiol. Rev., 1990, 70(4), 921-961.
[http://dx.doi.org/10.1152/physrev.1990.70.4.921] [PMID: 2217559]
[35]
Hernández, J.J.; Ragone, M.I.; Bonazzola, P.; Bandoni, A.L.; Consolini, A.E. Antitussive, antispasmodic, bronchodilating and cardiac inotropic effects of the essential oil from Blepharocalyx salicifolius leaves. J. Ethnopharmacol., 2018, 210, 107-117.
[http://dx.doi.org/10.1016/j.jep.2017.08.013] [PMID: 28811222]
[36]
Lima, F.J.; Brito, T.S.; Freire, W.B.; Costa, R.C.; Linhares, M.I.; Sousa, F.C.; Lahlou, S.; Leal-Cardoso, J.H.; Santos, A.A.; Magalhães, P.J. The essential oil of Eucalyptus tereticornis, and its constituents alpha- and beta-pinene, potentiate acetylcholine-induced contractions in isolated rat trachea. Fitoterapia, 2010, 81(6), 649-655.
[http://dx.doi.org/10.1016/j.fitote.2010.03.012] [PMID: 20302920]
[37]
Navarrete, A.; Ávila-Rosas, N.; Majín-León, M.; Balderas-López, J.L.; Alfaro-Romero, A.; Tavares-Carvalho, J.C. Mechanism of action of relaxant effect of Agastache mexicana ssp. mexicana essential oil in guinea-pig trachea smooth muscle. Pharm. Biol., 2017, 55(1), 96-100.
[http://dx.doi.org/10.1080/13880209.2016.1230140] [PMID: 27927103]
[38]
Vilela, D.A.D.; Silva, B.A.O.; Brito, M.C.; Menezes, P.M.N.; Bomfim, H.F.; Duarte-Filho, L.A.M.S.; Silva, T.R.D.S.; Ribeiro, L.A.A.; Lucchese, A.M.; Silva, F.S. Lippia alnifolia essential oil induces relaxation on Guinea-pig trachea by multiple pathways. J. Ethnopharmacol., 2020, 246, 112162.
[http://dx.doi.org/10.1016/j.jep.2019.112162] [PMID: 31419501]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy