Benzodiazepines influence melatonin secretion of the pineal organ of the trout in vitro.
The effect of benzodiazepines (BZP) on melatonin release was investigated in the pineal gland of the rainbow trout, Oncorhynchus mykiss, maintained under in vitro perifusion culture conditions. Melatonin and the methoxyindoles 5-methoxytryptophol (5-MTOL), 5-methoxyindoleacetic acid (5-MIAA), and 5-methoxytryptamine (5-MT) were determined directly in samples of the superfusion medium by HPLC with electrochemical detection. Melatonin release was significantly increased by addition of diazepam and clonazepam in a dose-related and reversible manner. The effects of benzodiazepines were more pronounced in light-adapted pineal organs, when melatonin secretion is low, than under scotopic conditions. When the perifusion medium was replaced by a medium containing low calcium, high magnesium concentrations, melatonin release was considerably decreased by 70% in light-adapted and 20% in dark-adapted pineal organs. Addition of diazepam to low Ca2+, high Mg(2+)-medium reversed the decrease of melatonin release and produced a clear rise in its secretion rate. Addition of the BZP antagonist flumazenil to the perifusion medium slightly decreased melatonin release in the light- and dark-adapted state, whereas the peripheral receptor antagonist PK 11195 did not alter melatonin release. The effect of diazepam is reduced by simultaneous addition of flumazenil to the superfusion medium, suggesting that the effects of diazepam are receptor-mediated. The methoxyindoles 5-MTOL, 5-MIAA, and 5-MT showed no significant changes of their release pattern after diazepam application in light- and dark-adapted pineal organs. These results suggest that BZP can influence melatonin production and release by an intrapineal action possibly on the melatonin synthesizing photoreceptor cell.
Meissl
H
H
Max-Planck-Institute for Physiol. and Clin. Res., W.G. Kerckhoff-Institute, Bad Nauheim, Germany.
Yáñez
J
J
Ekström
P
P
Grossmann
E
E
D008735:5-Methoxytryptamine / Q000378:metabolism; D000818:Animals; D001569:Benzodiazepines / Q000819:agonists / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium; D002998:Clonazepam / Q000494:pharmacology; D003470:Culture Media; D003623:Dark Adaptation; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008027:Light; D008274:Magnesium; D008550:Melatonin / Q000378:metabolism*; D017686:Oncorhynchus mykiss; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*
D003470:Culture Media; D007211:Indoles; D007546:Isoquinolines; D001569:Benzodiazepines; C001736:5-methoxyindoleacetic acid; D008735:5-Methoxytryptamine; D005442:Flumazenil; D006897:Hydroxyindoleacetic Acid; D002998:Clonazepam; C002465:methoxytryptophol; D008274:Magnesium; D008550:Melatonin; D003975:Diazepam; D002118:Calcium; C037850:PK 11195