Up-regulation of muscle uncoupling protein 3 gene expression by calcium channel blocker, benidipine hydrochloride in rats.
To examine whether benidipine hydrochloride, one of the calcium channel blockers, up-regulate uncoupling protein 3 (UCP3) expression in two skeletal muscles (gastrocnemius and soleus) in rats. Wistar rats were treated orally with benidipine hydrochloride at 4 mg/kg for 7 days. Blood pressure was measured after 4 days. At the end of experiments, the rats were weighed, and brown adipose tissue (BAT) and skeletal muscles (gastrocnemius and soleus muscles) were removed. The mRNA levels of uncoupling protein 1 (UCP1) and UCP3 were measured using the real-time quantitative reverse transcription-polymerase chain reaction method. Benidipine reduced body weight and also had a hypotensive effect. In rats treated with benidipine, UCP1 mRNA levels were significantly increased 1.4-fold in BAT, and UCP3 mRNA levels in BAT and gastrocnemius muscle were significantly increased 1.7 and 3.0-fold, respectively, compared with the control rats. There was no difference in UCP3 mRNA levels in soleus muscle between the two groups. We concluded that benidipine up-regulates not only UCP1 gene expression in BAT but also UCP3 gene expression in BAT and gastrocnemius muscle, which may contribute to thermogenesis in rats.
Sakane
Naoki
N
Department of Preventive Medicine, Clinical Research Institute, Center for Endocrine and Metabolic Disease, National Hospital Organization Kyoto Medical Center, Japan.
Kotani
Kazuhiko
K
Hioki
Chizuko
C
Yoshida
Toshihide
T
Kawada
Teruo
T
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004095:Dihydropyridines / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006851:Hydrochloric Acid / Q000737:chemistry; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3; D015854:Up-Regulation / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604373:Ucp1 protein, rat; C000604394:Ucp3 protein, rat; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3; C061004:benidipine; D006851:Hydrochloric Acid