Effects of ketamine on glucose uptake by glucose transporter type 3 expressed in Xenopus oocytes: The role of protein kinase C.
We investigated the effects of ketamine on the type 3 facilitative glucose transporter (GLUT3), which plays a major role in glucose transport across the plasma membrane of neurons. Human-cloned GLUT3 was expressed in Xenopus oocytes by injection of GLUT3 mRNA. GLUT3-mediated glucose uptake was examined by measuring oocyte radioactivity following incubation with 2-deoxy-d-[1,2-(3)H]glucose. While ketamine and S(+)-ketamine significantly increased GLUT3-mediated glucose uptake, this effect was biphasic such that higher concentrations of ketamine inhibited glucose uptake. Ketamine (10microM) significantly increased V(max) but not K(m) of GLUT3 for 2-deoxy-d-glucose. Although staurosporine (a protein kinase C inhibitor) increased glucose uptake, no additive or synergistic interactions were observed between staurosporine and racemic ketamine or S(+)-ketamine. Treatment with ketamine or S(+)-ketamine partially prevented GLUT3 inhibition by the protein kinase C activator phorbol-12-myrisate-13-acetate. Our results indicate that ketamine increases GLUT3 activity at clinically relevant doses through a mechanism involving PKC inhibition.
Tomioka
Shigemasa
S
Department of Dental Anesthesiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima City, Japan. tomioka@dent.tokushima-u.ac.jp
Kaneko
Miyuki
M
Satomura
Kazuhito
K
Mikyu
Tomiko
T
Nakajo
Nobuyoshi
N
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism*; D007649:Ketamine / Q000737:chemistry / Q000494:pharmacology*; D009865:Oocytes; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D013237:Stereoisomerism; D014982:Xenopus laevis
D051274:Glucose Transporter Type 3; D007649:Ketamine; D011493:Protein Kinase C; D005947:Glucose