title: Harmane: an atypical neurotransmitter?
abstract: Harmane is an active component of clonidine displacing substance and a candidate endogenous ligand for imidazoline binding sites. The neurochemistry of tritiated harmane was investigated in the present study examining its uptake and release properties in the rat brain central nervous system (CNS) in vitro. At physiological temperature, [(3)H]harmane was shown to be taken up in rat brain cortex. Further investigations demonstrated that treatment with monoamine uptake blockers (citalopram, nomifensine and nisoxetine) did not alter [(3)H]harmane uptake implicating that the route of [(3)H]harmane transport was distinct from the monoamine uptake systems. Furthermore, imidazoline ligands (rilmenidine, efaroxan, 2-BFI and idazoxan) showed no prominent effect on [(3)H]harmane uptake suggesting the lack of involvement of imidazoline binding sites. Subsequent analyses showed that disruption of the Na(+) gradient using ouabain or choline chloride did not block [(3)H]harmane uptake suggesting a Na(+)-independent transport mechanism. Moreover, higher temperatures (50°C) failed to impede [(3)H]harmane uptake implying a non-physiological transporter. The failure of potassium to evoke the release of preloaded [(3)H]harmane from rat brain cortex indicates that the properties of this putative endogenous ligand for imidazoline binding sites do not resemble that of a conventional neurotransmitter.
authors.affiliation: Psychopharmacology Unit, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK; General Education Department, American University of the Middle East, P.O. BOX 220 Dasman, 15453, Kuwait. Electronic address: Haya.Abu-Ghazaleh@aum.edu.kw.
authors.forename: Haya
authors.initials: H
authors.lastname: Abu Ghazaleh
authors.affiliation: Pharmacology Department, University of Alberta, Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Maggie D
authors.initials: MD
authors.lastname: Lalies
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, Burlington Danes Building, London W12 0NN, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Pharmacology Department, University of Alberta, Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hudson
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D006247:Harmine / Q000031:analogs & derivatives* / Q000378:metabolism; D048288:Imidazolines / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017208:Rats, Wistar
chemical_list: D048288:Imidazolines; D018377:Neurotransmitter Agents; D006247:Harmine; C005010:harman
keywords: Harmane; Monoamine; Release; Uptake; β-carboline