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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Physiol
2016 ; 7
(ä): 476
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Cannabinoid CB(1) Receptors Are Localized in Striated Muscle Mitochondria and
Regulate Mitochondrial Respiration
#MMPMID27826249
Mendizabal-Zubiaga J
; Melser S
; Bénard G
; Ramos A
; Reguero L
; Arrabal S
; Elezgarai I
; Gerrikagoitia I
; Suarez J
; Rodríguez De Fonseca F
; Puente N
; Marsicano G
; Grandes P
Front Physiol
2016[]; 7
(ä): 476
PMID27826249
show ga
The cannabinoid type 1 (CB(1)) receptor is widely distributed in the brain and
peripheral organs where it regulates cellular functions and metabolism. In the
brain, CB(1) is mainly localized on presynaptic axon terminals but is also found
on mitochondria (mtCB(1)), where it regulates cellular respiration and energy
production. Likewise, CB(1) is localized on muscle mitochondria, but very little
is known about it. The aim of this study was to further investigate in detail the
distribution and functional role of mtCB(1) in three different striated muscles.
Immunoelectron microscopy for CB(1) was used in skeletal muscles (gastrocnemius
and rectus abdominis) and myocardium from wild-type and CB(1) -KO mice.
Functional assessments were performed in mitochondria purified from the heart of
the mice and the mitochondrial oxygen consumption upon application of different
acute delta-9-tetrahydrocannabinol (?(9)-THC) concentrations (100 nM or 200 nM)
was monitored. About 26% of the mitochondrial profiles in gastrocnemius, 22% in
the rectus abdominis and 17% in the myocardium expressed CB(1). Furthermore, the
proportion of mtCB1 versus total CB(1) immunoparticles was about 60% in the
gastrocnemius, 55% in the rectus abdominis and 78% in the myocardium.
Importantly, the CB(1) immunolabeling pattern disappeared in muscles of CB(1) -KO
mice. Functionally, acute 100 nM or 200 nM THC treatment specifically decreased
mitochondria coupled respiration between 12 and 15% in wild-type isolated
mitochondria of myocardial muscles but no significant difference was noticed
between THC treated and vehicle in mitochondria isolated from CB(1) -KO heart.
Furthermore, gene expression of key enzymes involved in pyruvate synthesis,
tricarboxylic acid (TCA) cycle and mitochondrial respiratory chain was evaluated
in the striated muscle of CB(1) -WT and CB(1) -KO. CB(1) -KO showed an increase
in the gene expression of Eno3, Pkm2, and Pdha1, suggesting an increased
production of pyruvate. In contrast, no significant difference was observed in
the Sdha and Cox4i1 expression, between CB(1) -WT and CB(1) -KO. In conclusion,
CB(1) receptors in skeletal and myocardial muscles are predominantly localized in
mitochondria. The activation of mtCB(1) receptors may participate in the
mitochondrial regulation of the oxidative activity probably through the relevant
enzymes implicated in the pyruvate metabolism, a main substrate for TCA activity.