title: Glucose and glucose transporters regulate lymphatic pump activity through activation of the mitochondrial ATP-sensitive K+ channel.
abstract: We investigated the pivotal roles of glucose and its transporter in the regulation of mechanical activity of isolated rat thoracic ducts and then examined whether mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)) are involved in those responses. In the absence of extracellular glucose, the thoracic ducts showed pump activity during 120 min. Extracellular glucose caused a dose-dependent increase in the frequency of pump activity and a constriction in the thoracic ducts. Pump activity of the thoracic ducts in 0 mm glucose was completely inhibited in the presence of chlorogenic acid (an inhibitor of glucose-6-phosphatase). Cytochalasin B, an inhibitor of facilitative glucose transporter (GLUT), or phlorizin, an inhibitor of sodium-dependent glucose cotransporter (SGLT), significantly reduced the frequency of pump activity and dilated the thoracic ducts. A decrease in the frequency of pump activity induced by 5-hydroxydecanoate (5-HD, a selective blocker of mitoK(ATP)) was completely reversed by ruthenium red (an inhibitor of Ca(2+) uniporter in mitochondria). Diazoxide (a selective opener of mitoK(ATP)) significantly increased the frequency of pump activity. Carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP, a protonophore of mitochondrial proton pump action) significantly reduced the frequency of pump activity and dilated the thoracic ducts. Collectively, these findings suggest that glucose derived from intracellular glycogen and/or through GLUT/SGLT in lymphatic smooth muscles contributes to the regulation of the pump activity of isolated rat thoracic ducts, and that mitoK(ATP) in the cells may partially serve as a modulator of the mechanical functions associated with mitochondrial Ca(2+) uptake.
authors.affiliation: Department of Dentistry & Oral Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Li
authors.forename: Risuke
authors.initials: R
authors.lastname: Mizuno
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ono
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohhashi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002726:Chlorogenic Acid / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D010695:Phlorhizin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013897:Thoracic Duct / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D051246:Glucose Transport Proteins, Facilitative; D015221:Potassium Channels; D051247:Sodium-Glucose Transport Proteins; D014475:Uncoupling Agents; C117780:mitochondrial K(ATP) channel; D012430:Ruthenium Red; D002726:Chlorogenic Acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D003571:Cytochalasin B; D006003:Glycogen; D010695:Phlorhizin; D005952:Glucose-6-Phosphatase; D005947:Glucose; D003981:Diazoxide; D002118:Calcium