REGULATION OF NERVE GROWTH-FACTOR SECRETION IN L-M CELLS BY CATECHOL DERIVATIVES

We investigated the mechanism responsible for the stimulation of nerve growth factor (NGF) secretion by catechol derivatives in L-M cells, u sing L-threo-3,4-dihydroxyphenylserine (L-DOPS). Treatment of the cell s with L-DOPS increased the NGF content in the L-M cell medium by appr oximately 3-fold. This stimulatory effect was not blocked by a decarbo xylase inhibitor, or by alpha- or beta-adrenergic blockers. Intracellu lar cAMP levels were not changed by exposure to L-DOPS. The antioxidan ts, ascorbic acid and sodium pyrosulfite, completely prevented the sti mulatory effect of L-DOPS, and radical scavengers (superoxide dismutas e plus catalase) caused a significant partial inhibition of the respon se to L-DOPS. Quinone derivatives (adrenochrome, 4-n-propyl-1,2-benzoq uinone), which are the oxidative products of the catechol derivatives, increased the NGF content in the medium, and their potency was greate r than that of the catechol derivatives themselves. These findings sug gest that L-DOPS and other catechol derivatives might be oxidized in t he medium to form quinone derivatives, and that it is these which pred ominantly express a stimulatory effect on NGF secretion by a novel cAM P-independent mechanism in L-M cells.