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Anatomical distribution of sodium‐dependent [ 3 H]naloxone binding sites in rat brain
Author(s) -
SimSelley Laura J.,
Xiao Ruoyu,
Childers Steven R.
Publication year - 2000
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(20000315)35:4<256::aid-syn3>3.0.co;2-7
Subject(s) - (+) naloxone , chemistry , diprenorphine , interpeduncular nucleus , biophysics , stria terminalis , binding site , opioid receptor , receptor , lateral parabrachial nucleus , endocrinology , medicine , opioid , pharmacology , biochemistry , biology , central nervous system , parabrachial nucleus , midbrain
The sulfhydryl alkylating reagent N‐ethylmaleimide (NEM) blocks opioid receptor binding and receptor/G‐protein coupling. Sodium partially restores [ 3 H]naloxone binding after inhibition by NEM to reveal sodium‐dependent [ 3 H]naloxone sites, defined as binding in the presence of 50–100 mM NaCl after treatment of membranes or sections with 750 μM NEM. In the present study, receptor autoradiography of [ 3 H]naloxone binding in control and NEM‐treated tissue was used to examine the anatomical distribution of sodium‐dependent [ 3 H]naloxone sites in rat brain. In brain membranes, the pharmacology of sodium‐dependent [ 3 H]naloxone sites was consistent with that of mu opioid receptors. Relatively high IC 50 values for agonists and lack of effect of Gpp(NH)p on DAMGO displacement of [ 3 H]naloxone binding in NEM‐treated membranes indicated that the sodium‐dependent sites were low affinity sites, presumably uncoupled from G‐proteins. Autoradiograms revealed that NEM treatment dramatically reduced [ 3 H]naloxone binding in all brain regions. However, [ 3 H]naloxone binding was increased in specific regions in NEM‐treated sections in the presence of sodium, including bed nucleus of the stria terminalis, interpeduncular nucleus, periaqueductal gray, parabrachial nucleus, locus coeruleus, and commissural nucleus tractus solitarius. Sodium‐dependent [ 3 H]naloxone binding sites were not found in other areas that exhibited [ 3 H]naloxone binding in control tissue, including the striatum and thalamus. These studies revealed the presence of a subpopulation of [ 3 H]naloxone binding sites which are sodium‐dependent and have a unique regional distribution in the rat brain. Synapse 35:256–264, 2000. © 2000 Wiley‐Liss, Inc.