[Turnover of brain histamine and its changes by various drugs].
Histamine (HA) is synthesized from L-histidine by histidine decarboxylase (HDC), and HA released from neurons is predominantly methylated to tele-methylhistamine (t-MH), which is further metabolized by MAO. Therefore, the HA turnover rate is determined by either a exponential decrease in HA level after treatment with alpha-fluoromethylhistidine (alpha-FMH), a specific HDC inhibitor, or a linear accumulation of t-MH after pargyline treatment. Brain HA and t-MH can be simultaneously assayed using HPLC with fluorometric detection. Care should be given to avoid the contamination by extraencephalic mast-cell HA after microwave irradiation or immersion in liquid nitrogen, and to a marked circadian variation of t-MH level. The HA turnover is the highest in the hypothalamus, low in the pons-medulla oblongata and cerebellum, and nil in the spinal cord in rats, mice and guinea pigs. The half-life of neuronal HA is 8-87 min in various brain regions of these animals. Barbiturates, enflurane, benzodiazepines, GABA-mimetic drugs, ethanol and delta 9-tetrahydrocannabinol significantly decrease the HA turnover, whereas mu-opioid agonists such as morphine and [D-Ala2, MePhe4, Gly(ol)5] enkephalin enhance it. Foot-shock and phencyclidine also enhance it at least partly via mu-opioid receptors. Chlorpromazine, haloperidol, imipramine, methamphetamine or halothane have no influence on the HA turnover.
Oishi
R
R
Department of Pharmacology, Okayama University Medical School, Japan.
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002940:Circadian Rhythm; D013759:Dronabinol / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D006207:Half-Life; D006632:Histamine / Q000378:metabolism*; D008761:Methylhistamines / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*
D000777:Anesthetics; D008761:Methylhistamines; D010880:Piperidines; D011619:Psychotropic Drugs; D000431:Ethanol; D013759:Dronabinol; D006632:Histamine; C052075:thioperamide; C020404:tele-methylhistamine