Harmane an atypical neurotransmitter
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)Hharmane 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)Hharmane uptake implicating that the route of (3)Hharmane transport was distinct from the monoamine uptake systems. Furthermore, imidazoline ligands (rilmenidine, efaroxan, 2-BFI and idazoxan) showed no prominent effect on (3)Hharmane 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)Hharmane uptake suggesting a Na()-independent transport mechanism. Moreover, higher temperatures (50°C) failed to impede (3)Hharmane uptake implying a non-physiological transporter. The failure of potassium to evoke the release of preloaded (3)Hharmane 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.