title: Effects of ethanol on RhoA/Rho-kinase-mediated calcium sensitization in mouse lung parenchymal tissue.
abstract: Calcium sensitization by the RhoA/Rho-kinase (ROCK) pathway contributes to the contraction in smooth muscle. Contractile stimuli can sensitize myosin to Ca(2+) by activating RhoA/Rho-kinase that inhibits myosin light chain phosphatase activity. The present study was aimed at investigating the possible involvement of RhoA/Rho-kinase pathway in contractile responses to agonist (phenylephrine) and depolarizing (KCl) of mouse lung parenchymal tissues. Also, we investigated the effect of ethanol on RhoA/Rho-kinase pathway. Phenylephrine (10(-8)-10(-4) M) and KCl (10-80 mM) induced sustained contractions in parenchymal strips. Ethanol significantly attenuated the contractions to phenylephrine and KCl. The Rho-kinase inhibitors fasudil (5×10(-5) M) and Y-27632 (5×10(-5) M) inhibited contractions to in both control and ethanol-treated parenchymal strips. In addition, the relaxations induced by fasudil (10(-4) M) and Y-27632 (5×10(-4) M) on parenchymal strips contracted by phenylephrine but not KCl was decreased in ethanol-treatment group. Also, RhoA, ROCK1 and ROCK2 expressions were detected in mouse lung parenchymal tissue. In ethanol-treated group, expression of RhoA and ROCK1 but not ROCK2 decreased compared to control. Furthermore, ethanol causes apoptotic changes in alveolar type I epithelial cells of parenchymal tissue. These results suggest that RhoA/Rho-kinase signaling pathway plays an important role in phenylephrine- and KCl-induced Ca(2)(+) sensitization in mouse lung parenchymal tissue. Also, ethanol may be decrease phenylephrine- and KCl-induced contraction due to lowering the RhoA/Rho-kinase-mediated Ca(2+)-sensitizing by inhibiting RhoA/Rho-kinase pathway in parenchymal tissue. These results may be lead to important insights into the mechanisms of lung diseases due to alcohol consumption.
authors.affiliation: Department of Pharmacology, Pharmacy Faculty, Cukurova University, Adana, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Aydinoglu
authors.affiliation: Department of Pharmacology, Medical Faculty, Cukurova University, Adana, Turkey.
authors.forename: Olcay
authors.initials: O
authors.lastname: Ergurhan Kiroglu
authors.affiliation: Department of Plant and Animal Production, Mudurnu Süreyya Astarci Vocational School, Abant Izzet Baysal University, Bolu, Turkey.
authors.forename: Erhan
authors.initials: E
authors.lastname: Astarci
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Mersin University, Mersin, Turkey.
authors.forename: Ebru
authors.initials: E
authors.lastname: Balli
authors.affiliation: Department of Pharmacology, Medical Faculty, Cukurova University, Adana, Turkey. Electronic address: ogulener@gmail.com.
authors.forename: Nuran
authors.initials: N
authors.lastname: Ogulener
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine; D011189:Potassium Chloride; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000577:Amides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D010656:Phenylephrine; D000431:Ethanol; D011189:Potassium Chloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; C049347:fasudil; D002118:Calcium
keywords: Contraction; Ethanol; Fasudil; RhoA/Rho-kinase; Y-27632