Adiponectin Enhances Calcium Dependency of Mouse Bladder Contraction Mediated by Protein Kinase Ca 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 (AdipSen 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 mM) timeand 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 mM) of CCh, differences could not be detected with other CCh concentrations. However, the reduction in contraction under Ca-replaced conditions was significantly different between Adip-Sen and C57Bl mice (94.1 and 66.3% of normal contraction, respectively; n 5 5). A parameter of Ca sensitivity, the relation between intracellular Ca concentration and contraction, was increased in the AdipSen mouse, compared with that in the C57B1 mouse. This Ca 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, PKCa, was increased in the Adip-Sen mouse bladder, and CChinduced phosphorylation of PKCa 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 dependency of contraction mediated by PKCa expression.