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High‐Affinity Choline Transport Sites: Use of [ 3 H]Hemicholinium‐3 as a Quantitative Marker
Author(s) -
Happe H. Kevin,
Murrin L. Charles
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03277.x
Subject(s) - cholinergic , choline , in vivo , ligand (biochemistry) , radioligand , in vitro , acetylcholine , chemistry , binding site , cholinergic neuron , biochemistry , biology , pharmacology , receptor , neuroscience , genetics
High‐affinity choline transport (HAChT), the rate‐limiting and regulatory step in acetylcholine (ACh) synthesis, is selectively localized to cholinergic neurons. Hemicholinium‐3 (HC3), a potent and selective inhibitor of HAChT, has been used as a specific radioligand to quantify HAChT sites in membrane binding and autoradiographic studies. Because both HAChT velocity and [ 3 H]HC3 binding change as in vivo activity of cholinergic neurons is altered, these markers are also useful measures of cholinergic neuronal activity. Evidence that [ 3 H]HC3 is a specific ligand for HAChT sites on cholinergic terminals is reviewed. The ion requirements of HAChT and [ 3 H]HC3 binding indicate that sodium and chloride are required for recognition of both choline and [ 3 H]HC3. A common recognition site is also indicated by the close correspondence of the potency of HC3 and choline analogues for inhibiting both HAChT and [ 3 H]HC3 binding. The parallel regional distributions of both markers in adult brain, during development and after specific lesions, all indicate specific cholinergic localization. The close association of HAChT and [ 3 H]HC3 binding sites is also supported by parallel regulatory changes occurring after in vivo drug treatments and in vitro depolarization. Overall, the data indicate a close association between HAChT and [ 3 H]HC3 binding and are consistent with the sites being identical. Methodologic considerations in using [ 3 H]HC 3 as a ligand and considerations in interpretation of results are also discussed.