title: Phloridzin inhibits high K+-induced contraction via the inhibition of sodium: glucose cotransporter 1 in rat ileum.
abstract: Recent studies have shown that phloridzin, an inhibitor of sodium-glucose cotransporter (SGLT), strongly decreases high K+-induced contraction in phasic muscle, such as tenia coli, but slightly affects tonic muscle, such as trachea . In this study, we examined the inhibitory mechanism of phloridzin on high K+-induced muscle contraction in rat ileum, a phasic muscle. Phloridzin inhibited the high K+-induced contraction in the ileum and the aorta, and the relaxing effect of phloridzin at 1 mM in the ileum was approximately five-fold more potent than that in the aorta. The expression of SGLT1 mRNA in the ileum was higher than that of the aorta. Phloridzin significantly inhibited NADH/NAD ratio and phosphocreatine (PCr) content in the ileum; however, application of pyruvate recovered the inhibition of contraction and PCr content, but had no effect on ratio of NADH/NAD. High K+increased 2-(N (7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake in ileal smooth muscle cells, and phloridzin inhibited the increase in a concentration-dependent manner. These results suggest that phloridzin inhibits high K+-induced contraction because of the inhibition of energy metabolism via the inhibition of SGLT1.
authors.affiliation: Laboratory of Veterinary Pharmacology Nippon Veterinary and Life Science University, Kyonan-cho 1-chome, Musashino, Tokyo 180-862, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kanda
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kaneda
authors.forename: Akira
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Sasaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tajima
authors.forename: Norimoto
authors.initials: N
authors.lastname: Urakawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shimizu
authors.forename: Hiroetsu
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010695:Phlorhizin / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D017208:Rats, Wistar; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors*
chemical_list: D051269:Sodium-Glucose Transporter 1; D010695:Phlorhizin; D011188:Potassium