Selective inhibition by hydrocortisone of 3H-normetanephrine formation during 3H-transmitter release elicited by nerve stimulation in the isolated nerve-muscle preparation of the cat nictitating membrane.
The metabolism of 3H-noradrenaline released by nerve stimulation in the isolated nerve-muscle preparation of the cat nictitating membrane was determined under control conditions and in the presence of hydrocortisone, 28 muM, a concentration which inhibits the high affinity extraneuronal uptake of noradrenaline in this tissue. In the controls the main fraction in the overflow elicited by stimulation at 10 Hz during 2 min was the deaminated glycol, 3H-DOPEG (3,4-dihydroxyphenylglycol), which accounted for 45.2 +/- 2.96% of the total radioactivity. Under these conditions, 3H-noradrenaline represented 30.8 +/- 1.92%, while 3H-normetanephrine accounted for 14.5 +/- 0.94% of the total overflow of radioactivity. During exposure to hydrocortisone there was a selective inhibition in 3H-normetanephrine formation from 3H-noradrenaline released by stimulation while the other fractions were not affected significantly. In contrast to these results, there were no changes in the spontaneous outflow of 3H-normetanephrine during exposure to hydrocortisone. The results obtained support the view that 3H-normetanephrine in spontaneous release originates from the activity of prejunctional catechol-O-methyltransferase. On the other hand, 3H-normetanephrine formed during transmitter release elicited by nerve stimulation is due to the activity of extraneuronal catechol-O-methyltransferase. Access of 3H-noradrenaline released by nerve stimulation to extraneuronal catechol-O-methyltransferase is mediated through the high-affinity, hydrocortisone-sensitive extraneuronal uptake mechanism.
D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000502:physiology; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D006018:Glycols / Q000096:biosynthesis; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D008333:Mandelic Acids / Q000096:biosynthesis; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects; D009541:Nictitating Membrane / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000096:biosynthesis*; D010646:Phentolamine / Q000494:pharmacology; D014316:Tritium
D006018:Glycols; D008333:Mandelic Acids; D009647:Normetanephrine; D014316:Tritium; D002394:Catechol O-Methyltransferase; D006854:Hydrocortisone; D009638:Norepinephrine; D010646:Phentolamine