In vivo assessment of catechol O-methyltransferase activity in rabbit skeletal muscle

With the use of microdialysis technique in the anesthetized rabbit, we examined the catechol O-methyltransferase (COMT) activity at the skeletal muscle interstitium. We implanted a dialysis probe into the adductor muscle, and monitored dialysate catecholamines and their metabolites with chromatogram-electrochemical detection. Administration of COMT inhibitor (entacapone) decreased dialysate 3-methoxy 4-hydroxyphenylglycol (MHPG) levels. Local administration of dihydroxyphenylglycol induced increases in dialysate MHPG levels. These increases in dialysate MHPG levels were suppressed by the addition of entacapone. The concentration of MHPG in the skeletal muscle dialysate corresponded to the COMT activity in the skeletal muscle. Furthermore, local administration of norepinephrine or epinephrine increased normetanephrine or metanephrine levels in dialysate but not MHPG levels. Skeletal muscle microdialysis with local administration of catecholamine offers a new method for in vivo assessment of regional COMT activity.