Effects of adrenergic blockers or bicuculline on diazepam induced changes in rat pineal melatonin synthesis in vivo and in vitro.
The effect of propranolol (PPL), phenoxybenzamine (PBZ) or bicuculline (BCL) on the diazepam (DZP)-induced changes of pineal melatonin synthesis in male rats was examined in vivo and in vitro. Administration of PBZ did not affect the inhibitory action of DZP on pineal melatonin synthesis in vivo. A single injection of PPL inhibited the pineal melatonin synthesis similarly to the administration of DZP alone, but the two drugs together did not exhibit additive or synergistic effects on the melatonin synthesis. Significant decreases in the N-acetyltransferase (NAT) activity and the N-acetylserotonin (NAS) and melatonin contents were observed in the BCL-injected group, being greater than those in the DZP-treated group. Unexpectedly, however, the combination treatment of DZP and BCL causes an increase in the NAT activity and melatonin content compared with the BCL-alone group. Incubation with DZP at higher concentrations resulted in an increase of pineal NAT activity in vitro, but this increase was inhibited by preincubation with PPL, PBZ or BCL. DZP treatment thus appeared to have different effects on pineal NAT activity in vivo and in vitro. These results suggest that both a GABAergic mechanism and peripheral benzodiazepine (BZP) receptors in rat pineal gland may be involved in the modulation of melatonin synthesis by DZP.
Wakabayashi
H
H
Department of Analytical Chemistry, Niigata College of Pharmacy, Japan.
Shimada
K
K
Satoh
T
T
D000121:Acetylserotonin O-Methyltransferase / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D010643:Phenoxybenzamine / Q000494:pharmacology*; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D010643:Phenoxybenzamine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D011433:Propranolol; D000121:Acetylserotonin O-Methyltransferase; D008550:Melatonin; C006389:N-acetylserotonin; D003975:Diazepam; D001640:Bicuculline