Relaxant effect of ghrelin on guinea pig isolated tracheal smooth muscle: role of epithelial NO and PGE2
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This study aimed at investigating the potential ghrelin relaxing effect on guinea pig isolated tracheal smooth muscle (TSM). Using an in vitro experimental approach, the physiological role of the airway epithelium on smooth muscle relaxation has been investigated by analyzing the dose-response curves for carbachol- or histamine-induced contractions on epithelium intact versus denuded tracheal tissue. The relaxant effect of ghrelin (5–200 μmol/L) then investigated on carbachol-contracted, non-sensitized, and ovalbumin (OVA)-sensitized guinea pig TSM with an intact or denuded epithelium. The isolated TSMs from identical guinea pigs were incubated in Krebs solution aerated with 95% O2 and 5% CO2 through an automated tissue organ bath system (n = 6 for each group). The ghrelin relaxation mechanism was assessed by adding L-NAME, indomethacin, and YIL-781 for GHS-R1 into the tissue chamber. The spasmogens carbachol and histamine have shown a significantly higher contracting effect on epithelium-denuded than in epithelium-intact TSM confirmed by the significantly higher mean pEC50 of both agonists on the epithelium-denuded trachea (p < 0.05). Ghrelin has shown a concentration-dependent relaxing effect on carbachol-contracted TSM (r = 0.96, p = 0.00). The effect was more evident in the intact non-sensitized than in epithelium-denuded or OVA-sensitized groups (p < 0.05). Preincubation with nitric oxide (NO) and prostaglandin E2 (PGE2) inhibitors has significantly reduced the ghrelin-induced relaxation on epithelium-intact TSM suggesting an epithelium-dependant mechanism. However, GHS-R1a antagonist has also succeeded to reduce ghrelin relaxant effect, which needs further clarification. Ghrelin proved to have a potential TSM relaxant effect possibly through epithelium-dependant mechanisms involving NO and PGE2.
KeywordsGhrelin Guinea pig Smooth muscles Epithelial NO PGE2
I would like to acknowledge Dr. Aamir Magzoub & Dr. AdilWaddad (College of Medicine), Mr. Ibrahim Shaikh & Mr. Mohammed ShafiuddinHabeeb (College of Pharmacy), Najran University for their valuable assistance in this work.
This study was supported by King Abdulaziz City for Science and Technology (KACST) for funding this project with No. A.T.34/116.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The study was ethically approved by the research ethics committee at the College of Medicine, Najran University, Kingdom of Saudi Arabia.
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