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α7 Nicotinic acetylcholine receptor contributes to the alleviation of lung ischemia-reperfusion injury by transient receptor potential vanilloid type 1 stimulation.
- Source :
-
The Journal of surgical research [J Surg Res] 2018 Oct; Vol. 230, pp. 164-174. Date of Electronic Publication: 2018 Jun 23. - Publication Year :
- 2018
-
Abstract
- Background: Activation of transient receptor potential vanilloid type 1 (TRPV1) decreases lung ischemia-reperfusion injury (LIRI) in rabbits and rats. Stimulation of α7 nicotinic acetylcholine receptors (α7nAChRs) protects against lung injury. Here we examined whether α7nAChRs contribute to TRPV1-mediated protection against LIRI.<br />Methods: Wild-type (WT) and TRPV1-knockout (KO) mice were subjected to 1-h lung ischemia by clamping left hilum, followed by 2-h reperfusion. WT or KO mice were pretreated with vehicle, TRPV1 agonist capsaicin, TRPV1 antagonist capsazepine, α7nAChR antagonist methyllycaconitine, or α7nAChR agonist PNU-282987. Arterial blood and lung tissues were obtained for blood gas, lung wet-to-dry weight ratio, interleukin (IL)1β, IL6, tumor necrosis factor-α (TNF-α), apoptosis-related proteins (caspases, Bax, Fas), and pathologic scoring.<br />Results: Capsaicin pretreatment reduced wet-to-dry ratio, pathologic score, alveolar-arterial oxygen gradient (A-aDO <subscript>2</subscript> ), and IL1β, IL6, and TNFα levels in WT mice, with no effects in KO mice. This reduction was reversed by TRPV1 blockade. Furthermore, α7nAChR blockade before capsaicin exacerbated LIRI as evidenced by enhanced alveolar-arterial oxygen gradient, pathologic score, and IL1β, IL6, and TNFα levels, while α7nAChR agonist pretreatment under TRPV1 blockade showed opposite changes. Capsaicin also decreased cleaved caspase-3, caspase-3/9, and Bax protein expression, effects abolished by TRPV1 blockade. Similarly, α7nAChR blockade diminished capsaicin-induced downregulation of apoptotic proteins, and α7nAChR activation decreased expression levels even under TRPV1 blockade.<br />Conclusions: TRPV1 activation alleviates LIRI, partially dependent on α7nAChR activity. The α7nAChR stimulation with or without existence of TRPV1 alleviates LIRI. Thus, α7nAChR is involved in the pathway of TRPV1-mediated protection against LIRI and the specific mechanism remains to be revealed.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Aconitine analogs & derivatives
Aconitine pharmacology
Animals
Apoptosis drug effects
Benzamides metabolism
Bridged Bicyclo Compounds metabolism
Capsaicin analogs & derivatives
Capsaicin therapeutic use
Disease Models, Animal
Down-Regulation
Humans
Lung drug effects
Lung metabolism
Lung pathology
Lung Injury pathology
Male
Mice
Mice, Knockout
Reperfusion Injury etiology
Reperfusion Injury pathology
TRPV Cation Channels agonists
TRPV Cation Channels antagonists & inhibitors
TRPV Cation Channels genetics
Treatment Outcome
alpha7 Nicotinic Acetylcholine Receptor agonists
alpha7 Nicotinic Acetylcholine Receptor antagonists & inhibitors
Capsaicin pharmacology
Lung Injury drug therapy
Reperfusion Injury drug therapy
TRPV Cation Channels metabolism
alpha7 Nicotinic Acetylcholine Receptor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8673
- Volume :
- 230
- Database :
- MEDLINE
- Journal :
- The Journal of surgical research
- Publication Type :
- Academic Journal
- Accession number :
- 30100034
- Full Text :
- https://doi.org/10.1016/j.jss.2018.05.038