title: Dexmedetomidine-Induced Contraction Involves CPI-17 Phosphorylation in Isolated Rat Aortas.
abstract: Dexmedetomidine, a highly selective α-2 adrenoceptor agonist, produces vasoconstriction, which leads to transiently increased blood pressure. The goal of this study was to investigate specific protein kinases and the associated cellular signal pathways responsible for the increased calcium sensitization induced by dexmedetomidine in isolated rat aortas, with a particular focus on phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17). The effect of Y-27632 and chelerythrine on the dexmedetomidine-induced intracellular calcium concentration ([Ca2+]i) and tension were assessed using fura-2-loaded aortic strips. The effects of rauwolscine, Y-27632, chelerythrine, and ML-7 hydrochloride on the dexmedetomidine-induced phosphorylation of CPI-17 or of the 20-kDa regulatory light chain of myosin (MLC20) were investigated in rat aortic vascular smooth muscle cells. The effects of rauwolscine, Y-27632, and chelerythrine on the membrane translocation of Rho-kinase and protein kinase C (PKC) phosphorylation induced by dexmedetomidine were assessed. Y-27632 and chelerythrine each reduced the slopes of the [Ca2+]i-tension curves of dexmedetomidine-induced contraction, and Y-27632 more strongly reduced these slopes than did chelerythrine. Rauwolscine, Y-27632, chelerythrine, and ML-7 hydrochloride attenuated the dexmedetomidine-induced phosphorylation of CPI-17 and MLC20. Taken together, these results suggest that dexmedetomidine-induced contraction involves calcium sensitization, which appears to be mediated by CPI-17 phosphorylation via Rho-kinase or PKC.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si 52727, Korea. mdoksh@naver.com.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.affiliation: Department of Physiology, Institute for Clinical and Translational Research, Catholic Kwandong University College of Medicine, Gangneung 25601, Korea. skwon2028@cku.ac.kr.
authors.forename: Seong-Chun
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: Department of Anesthesiology and Pain Medicine, Pusan National University Hospital, Biomed Research Institute, Pusan National University School of Medicine, Busan 49241, Korea. jidal75@naver.com.
authors.forename: Jiseok
authors.initials: J
authors.lastname: Baik
authors.affiliation: Department of Anesthesiology and Pain Medicine, Pusan National University Hospital, Biomed Research Institute, Pusan National University School of Medicine, Busan 49241, Korea. ccarrot@daum.net.
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Hong
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju-si 52727, Korea. wldk0430@gmail.com.
authors.forename: Jiah
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea. taszzang@hanmail.net.
authors.forename: Jeong Yeol
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si 52727, Korea. jtsohn@nongae.gsnu.ac.kr.|Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea. jtsohn@nongae.gsnu.ac.kr.
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053119:Benzophenanthridines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D020927:Dexmedetomidine / Q000494:pharmacology*; D016257:Fura-2 / Q000737:chemistry; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009124:Muscle Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015016:Yohimbine / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000577:Amides; D053119:Benzophenanthridines; D009124:Muscle Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; C491519:Ppp1r14a protein, rat; D011725:Pyridines; C108830:Y 27632; D015016:Yohimbine; D020927:Dexmedetomidine; C016299:chelerythrine; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D002118:Calcium; D016257:Fura-2
keywords: Rho-kinase; aorta; calcium sensitization; dexmedetomidine; phosphorylation-dependent inhibitory protein of myosin phosphatase; protein kinase C