We have investigated the possibility that the synthesis/accumulation of neurosteroids, i.e., brain-produced steroids putatively endowed with modulatory actions in the CNS, is regulated by monoaminergic receptor-mediated mechanisms. In minces of rat brain cortex, L-ascorbic acid concentration-dependently (0.07-1.0 mM) increases the levels of pregnenolone, allotetrahydrodeoxycorticosterone, and dehydroepiandrosterone. This effect of L-ascorbic acid is region-dependent: in hippocampus, progesterone and allopregnanolone are also increased, whereas dehydroepiandrosterone is unchanged, and in corpus striatum only progesterone is increased significantly. 5-Hydroxytryptamine (10 microM), 1-(3-chlorophenyl)piperazine (1.0 microM), and 5-methoxytryptamine (0.4 microM) mimic the effect of L-ascorbic acid, whereas a pretreatment with p-chlorophenylalanine (400 mg/kg i.p., 2 days) reduces the amplitude of the L-ascorbic acid effect on brain cortical neurosteroids. The effect of L-ascorbic acid is blocked by the nonselective serotonin antagonists methiothepin, clozapine, methysergide, and pizotifen, but not mesulergine, spiperone, MDL 72222, and DL-propranolol, nor by the catecholaminergic receptor antagonists prazosin and S(-)-sulpiride. L-Ascorbic acid is not additive with dibutyryl-cyclic AMP and, furthermore, the inhibition of adenylate cyclase by MDL 12330A, but not of phospholipase C by U-73122, markedly attenuates the L-ascorbic acid-induced increase of pregnenolone in rat brain cortical minces. Together these data suggest that L-ascorbic acid plays a role in the modulation of neurosteroidogenesis, presumably by favoring the activation of the purported serotonin type 6 receptor by endogenous serotonin.

Roscetti, G., Del Carmine, R., Trabucchi, M., Massotti, M., Purdy, R.H., & Barbaccia, M.L. (1998). Modulation of neurosteroid synthesis/accumulation by L-ascorbic acid in rat brain tissue: inhibition by selected serotonin antagonists. JOURNAL OF NEUROCHEMISTRY, 71(3), 1108-1117.

Modulation of neurosteroid synthesis/accumulation by L-ascorbic acid in rat brain tissue: inhibition by selected serotonin antagonists

ROSCETTI, GIANNA;DEL CARMINE, RENATA;TRABUCCHI, MARCO MARIO;BARBACCIA, MARIA LUISA
1998-09

Abstract

We have investigated the possibility that the synthesis/accumulation of neurosteroids, i.e., brain-produced steroids putatively endowed with modulatory actions in the CNS, is regulated by monoaminergic receptor-mediated mechanisms. In minces of rat brain cortex, L-ascorbic acid concentration-dependently (0.07-1.0 mM) increases the levels of pregnenolone, allotetrahydrodeoxycorticosterone, and dehydroepiandrosterone. This effect of L-ascorbic acid is region-dependent: in hippocampus, progesterone and allopregnanolone are also increased, whereas dehydroepiandrosterone is unchanged, and in corpus striatum only progesterone is increased significantly. 5-Hydroxytryptamine (10 microM), 1-(3-chlorophenyl)piperazine (1.0 microM), and 5-methoxytryptamine (0.4 microM) mimic the effect of L-ascorbic acid, whereas a pretreatment with p-chlorophenylalanine (400 mg/kg i.p., 2 days) reduces the amplitude of the L-ascorbic acid effect on brain cortical neurosteroids. The effect of L-ascorbic acid is blocked by the nonselective serotonin antagonists methiothepin, clozapine, methysergide, and pizotifen, but not mesulergine, spiperone, MDL 72222, and DL-propranolol, nor by the catecholaminergic receptor antagonists prazosin and S(-)-sulpiride. L-Ascorbic acid is not additive with dibutyryl-cyclic AMP and, furthermore, the inhibition of adenylate cyclase by MDL 12330A, but not of phospholipase C by U-73122, markedly attenuates the L-ascorbic acid-induced increase of pregnenolone in rat brain cortical minces. Together these data suggest that L-ascorbic acid plays a role in the modulation of neurosteroidogenesis, presumably by favoring the activation of the purported serotonin type 6 receptor by endogenous serotonin.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14
English
Con Impact Factor ISI
Hippocampus; Hormones; Male; Serotonin Agents; Hormone Antagonists; Fenclonine; Adenylate Cyclase; Ascorbic Acid; Pregnenolone; Rats; Animals; Serotonin; Cerebral Cortex; Rats, Sprague-Dawley; Brain; Serotonin Antagonists
Roscetti, G., Del Carmine, R., Trabucchi, M., Massotti, M., Purdy, R.H., & Barbaccia, M.L. (1998). Modulation of neurosteroid synthesis/accumulation by L-ascorbic acid in rat brain tissue: inhibition by selected serotonin antagonists. JOURNAL OF NEUROCHEMISTRY, 71(3), 1108-1117.
Roscetti, G; DEL CARMINE, R; Trabucchi, Mm; Massotti, M; Purdy, R; Barbaccia, Ml
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/14856
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 19
social impact