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Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions

Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 2960; https://doi.org/10.3390/ijms19102960
Received: 5 September 2018 / Revised: 23 September 2018 / Accepted: 26 September 2018 / Published: 28 September 2018
(This article belongs to the Section Biochemistry)
Carbon monoxide (CO) has been reported to contribute to the maintenance of gastric mucosal integrity, gastroprotection, and ulcer healing. However, involvement of transient receptor potential vanilloid receptor type 1 (TRPV1) located on afferent sensory fibers endings and sensory neuropeptide calcitonin gene-related peptide (CGRP) in CO-mediated gastroprotection against ethanol-induced gastric damage has not been explored. Male Wistar rats with and without denervation of afferent sensory neurons induced by capsaicin (total dose 125 mg/kg within 3 days) were pretreated with vehicle, CO donor tricarbonyldichlororuthenium (II) dimer (CORM-2, 5 mg/kg i.g.), administered alone or with CGRP-α (10 μg/kg i.p.) or TRPV1 antagonist capsazepine (5 mg/kg i.g.), followed 30 min later by intragastric (i.g.) administration of 75% ethanol. The area of gastric damage and gastric blood flow (GBF) were assessed planimetrically and by laser flowmetry, respectively. Microscopic evaluation of ethanol-induced gastric lesions was performed after haematoxylin/eosin (H&E) or alcian blue/periodic acid-Schiff/alcian blue (AB/PAS) staining. Gastric mucosal mRNA fold change for heme oxygenase (HMOX)-1, HMOX-2, CGRP-α, CGRP-β, inducible nitric oxide synthase (iNOS), endothelial (e)NOS, neuronal (n)NOS, cyclooxygenase (COX)-1, COX-2, and protein expression for HMOX-1 and TRPV1 was determined by real-time PCR or Western blot, respectively. Pretreatment with CORM-2 combined or not with CGRP reduced ethanol-induced gastric lesions and elevated GBF. Capsaicin-denervation or co-treatment with capsazepine or CGRP and CORM-2 in capsaicin-denervated animals failed to affect these beneficial effects of CO donor. In rats with intact sensory nerves, CORM-2 increased gastric mRNA level for HMOX-1 and CGRP-α. In capsaicin-denervated rats, CORM-2 increased eNOS mRNA fold change and TRPV1 protein expression while capsaicin denervation itself decreased HMOX-1 protein expression and eNOS mRNA level. We conclude that CO prevents gastric mucosa from ethanol-induced lesions due to activation of TRPV1/CGRP-α system and accompanying increase in gastric microcirculation but independently on afferent sensory nerve activity despite the stimulation of TRPV1 protein and CGRP-α mRNA expression. View Full-Text
Keywords: carbon monoxide; gastric mucosa; transient receptor potential vanilloid receptor type 1; calcitonin gene-related peptide carbon monoxide; gastric mucosa; transient receptor potential vanilloid receptor type 1; calcitonin gene-related peptide
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MDPI and ACS Style

Magierowska, K.; Wojcik, D.; Chmura, A.; Bakalarz, D.; Wierdak, M.; Kwiecien, S.; Sliwowski, Z.; Brzozowski, T.; Magierowski, M. Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions. Int. J. Mol. Sci. 2018, 19, 2960. https://doi.org/10.3390/ijms19102960

AMA Style

Magierowska K, Wojcik D, Chmura A, Bakalarz D, Wierdak M, Kwiecien S, Sliwowski Z, Brzozowski T, Magierowski M. Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions. International Journal of Molecular Sciences. 2018; 19(10):2960. https://doi.org/10.3390/ijms19102960

Chicago/Turabian Style

Magierowska, Katarzyna, Dagmara Wojcik, Anna Chmura, Dominik Bakalarz, Mateusz Wierdak, Slawomir Kwiecien, Zbigniew Sliwowski, Tomasz Brzozowski, and Marcin Magierowski. 2018. "Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions" International Journal of Molecular Sciences 19, no. 10: 2960. https://doi.org/10.3390/ijms19102960

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