Adiponectin enhances calcium dependency of mouse bladder contraction mediated by protein kinase Cα expression.
Adiponectin is an adipose tissue-secreted protein and is a multifunctional adipocytokine. However, the association of adiponectin with bladder contraction has not been investigated. In this study, the adiponectin-sense transgenic mouse (Adip-Sen mouse; age, 16-24 weeks; male) and age-matched controls (C57Bl mouse) were studied. The Adip-Sen mouse showed a significant increase in plasma adiponectin levels (56.2%; P < 0.01), compared with those in the C57Bl mouse, without affecting other lipid parameters. Isometric force development in bladder smooth muscle tissues were detected using an organ-bath system. Although carbachol (CCh)-induced (0.1-100 µM) time- and dose-dependent contractions in Adip-Sen mouse bladder were slightly enhanced, compared with those in the C57Bl mouse during a low range (0.3-1.0 µM) of CCh, differences could not be detected with other CCh concentrations. However, the reduction in contraction under Ca(2+)-replaced conditions was significantly different between Adip-Sen and C57Bl mice (94.1 and 66.3% of normal contraction, respectively; n = 5). A parameter of Ca(2+) sensitivity, the relation between intracellular Ca(2+) concentration and contraction, was increased in the Adip-Sen mouse, compared with that in the C57B1 mouse. This Ca(2+) dependency in the Adip-Sen mouse was reduced by a protein kinase C (PKC) inhibitor, but not by a Rho kinase inhibitor. Expression of the calcium-dependent isoform of PKC, PKCα, was increased in the Adip-Sen mouse bladder, and CCh-induced phosphorylation of PKCα was also enhanced, compared with those in the C57Bl mouse. In conclusion, adiponectin is associated with bladder smooth muscle contraction, which involves an increase in Ca(2+) dependency of contraction mediated by PKCα expression.
Department of Pharmacology, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. kojinobe@pharm.showa-u.ac.jp
Koji
K
Nobe
Akiko
A
Fujii
Kiyomi
K
Saito
Takaharu
T
Negoro
Yoshio
Y
Ogawa
Yasuko
Y
Nakano
Terumasa
T
Hashimoto
Kazuo
K
Honda
D052242:Adiponectin / Q000097:blood / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects* / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D051571:Protein Kinase C-alpha / Q000096:biosynthesis*; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology
D052242:Adiponectin; D008055:Lipids; D002217:Carbachol; D051571:Protein Kinase C-alpha; D005947:Glucose; D002122:Calcium Chloride; D002118:Calcium