[(125)I]LSD binding to serotonin and dopamine receptors in bovine caudate membranes.
[(125)I]LSD (labeled at the 2 position) has been introduced as the first (125)I-labeled ligand for serotonin 5-HT(2) (S2) receptors. In the present study we examined the binding of [(125)I]LSD and its non-radioactive homologue, 2I-LSD, to bovine caudate homogenates. The binding of [(125)I]LSD is saturable, reversible, stereospecific and is destroyed by boiling the membranes. The specific to total binding ratio in this tissue is 75-80% and Scatchard plots of the binding data reveal K(d) = 1.1 nM, B(max) = 9.6 fmol/mg wet weight tissue. The association and dissociation rate constants are highly temperature dependent. At 0 degrees C the net dissociation is less than 5% after 1 h and the association rate is proportionately slow. IC(50) values for a variety of compounds show a clear 5-HT(2) (S2) serotonergic pattern at this [(125)I]LSD site. Blockage of this primary 5-HT(2) (S2) caudate binding site by 0.3 ?M mianserin reveals the presence of a weaker [(125)I]LSD binding site with a K(d) = 9.1 nM, B(max) = 7.6 fmol/mg tissue. This secondary site is a D3 dopaminergic receptor site, as shown by the relative abilities of various displacers to inhibit this binding. Binding studies with nonradioactive 2I-LSD reveal a clear preference for D2 over D3 dopamine receptor sites. [(125)I]LSD is a sensitive and selective label for 5-HT(2) (S2) serotonin receptor sites in both rat frontal cortex and bovine caudate membranes. Blockage of the primary bovine caudate [(125)I]LSD binding site with mianserin allows the high sensitivity of [(125)I]LSD to be applied to D2 dopamine receptor studies as well.
Hartig
P R
PR
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, U.S.A.
Evans
M J
MJ
Krohn
A M
AM
Leder
S A
SA
Sze
P C
PC
Stoffers
D A
DA