The tyramine binding site in the central nervous system: an overview.
The [3H]Tyramine (TY) binding site is proposed as a high affinity marker of the membrane carrier for dopamine (DA) in synaptic vesicles from DA-rich brain regions. Under precise assay conditions, there is neither a consistent association of TY with the neuronal, cocaine-sensitive DA transporter, nor with mitochondrial or microsomal targets. TY-labeled sites have a high affinity for selected toxins such as the Parkinsonian agent MPP+ (1-methyl-4-phenylpyridinium ion), or drugs such as diphenylalkylamine Ca(2+)-channel antagonists. The MPP+/TY site interaction, which in the striatum leads to depletion of vesicular DA, occurs in dopaminergic as well as in noradrenergic regions, though with different kinetic profiles. TY-labeled carriers for DA and noradrenaline (NA) in respective vesicles seem to be different entities, which might result in a region-specific rate of toxin sequestration and/or release from heterogeneous vesicles. Whereas MPP+ is a potent competitive-type inhibitor of [3H]TY binding, prenylamine-like Ca(2+)-channel antagonists can compete with TY for the vesicle site, in a tetrabenazine- or reserpine-like manner, and also inhibit TY binding thanks to the extra-channel directed impairment of membrane bioenergetics they are proposed to provoke. This follows from the generally-accepted assumption that similar mechanisms are operational for secretory organelles in adrenals and CNS, and from the marked sensitivity of TY binding to miscellaneous energy-disrupting agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neuroscience, B. Brodie, Cagliari, Italy.
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Vaccari
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D017982:Receptors, Biogenic Amine; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D014439:Tyramine / Q000378:metabolism*
D002121:Calcium Channel Blockers; D017982:Receptors, Biogenic Amine; D017981:Receptors, Neurotransmitter; C066175:tyramine receptor; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D014439:Tyramine