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, using L-threo-3,4-dihydroxyphenylserine (L-DOPS). Treatment of the cells with L-DOPS increased the NGF content in the L-M cell medium by approximately 3-fold. This stimulatory effect was not blocked by a decarboxylase inhibitor, or by alpha- or beta-adrenergic blockers. Intracellular cAMP levels were not changed by exposure to L-DOPS. The antioxidants, ascorbic acid and sodium pyrosulfite, completely prevented the stimulatory effect of L-DOPS, and radical scavengers (superoxide dismutase plus catalase) caused a significant partial inhibition of the response to L-DOPS. Quinone derivatives (adrenochrome, 4-n-propyl-1,2-benzoquinone), which are the oxidative products of the catechol derivatives, increased the NGF content in the medium, and their potency was greater than that of the catechol derivatives themselves. These findings suggest that L-DOPS and other catechol derivatives might be oxidized in the medium to form quinone derivatives, and that it is these which predominantly express a stimulatory effect on NGF secretion by a novel cAMP-independent mechanism in L-M cells.
Murakami
A
A
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Tatsuno
T
T
Kimura
T
T
Noguchi
H
H
Nakamura
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology*; D002460:Cell Line; D015103:Droxidopa / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D016166:Free Radical Scavengers; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D013268:Stimulation, Chemical
D000975:Antioxidants; D002396:Catechols; D016166:Free Radical Scavengers; D009414:Nerve Growth Factors; D011809:Quinones; D015103:Droxidopa