TY - JOUR
T1 - Stereospecific binding of d-lysergic acid diethylamide (LSD) to brain membranes
T2 - Relationship to serotonin receptors
AU - Bennett, James P.
AU - Snyder, Solomon H.
N1 - Funding Information:
This work was supported by USPHS Fellowship 5TO1GM0062414 and a summer fellowship from the Epilepsy Foundation of America to J.P.B. and USPHS Grant DA-00266 and RSDA Award MH-33128 to S.H.S., and by the Benevolent Foundation of Scottish Rite Freemasonry, Northern Jurisdiction, U.S.A.
PY - 1975/9/5
Y1 - 1975/9/5
N2 - d-[3H]LSD binds saturably, reversibly, and with a high affinity (KD = 10 nM) to rat brain membranes. The association and dissociation rates of binding are temperature dependent and fastest at 37 °C. Binding is enriched in crude microsomal (P3) membranes. d-[3H]LSD binding is stereospecific as l-LSD, the psychotropically inactive enantiomer, is 1000 times weaker than d-LSD as a displacing agent. The potencies of other LSD analogues parallel their psychotropic activity with the exception of 2-bromo-LSD (psychotropically inactive) which is as potent as d-LSD in displacing bound d-[3H]LSD. Serotonin is the only putative neurotransmitter with affinity (ED50 = 3 μM) for the LSD binding site, and psychotropically active alkylindoleamines are also potent displacing agents. Destruction of presynaptic serotonin neuronal elements by lesioning the midbrain raphe nuclei does not change the affinity or maximum number of detectable in vitro d-[3H]LSD binding sites. The regional distribution in monkey brain of d-[3H]LSD binding and high affinity [3H]serotonin uptake, a marker for pre-synaptic serotonin nerve terminal density, shows some correlation. The most notable exceptions are cerebral cortical areas which are highest in d-[3H]LSD binding and only intermediate in [3H]serotonin uptake. Our evidence suggests that d-[3H]LSD binds to post-synaptic serotonin receptors.
AB - d-[3H]LSD binds saturably, reversibly, and with a high affinity (KD = 10 nM) to rat brain membranes. The association and dissociation rates of binding are temperature dependent and fastest at 37 °C. Binding is enriched in crude microsomal (P3) membranes. d-[3H]LSD binding is stereospecific as l-LSD, the psychotropically inactive enantiomer, is 1000 times weaker than d-LSD as a displacing agent. The potencies of other LSD analogues parallel their psychotropic activity with the exception of 2-bromo-LSD (psychotropically inactive) which is as potent as d-LSD in displacing bound d-[3H]LSD. Serotonin is the only putative neurotransmitter with affinity (ED50 = 3 μM) for the LSD binding site, and psychotropically active alkylindoleamines are also potent displacing agents. Destruction of presynaptic serotonin neuronal elements by lesioning the midbrain raphe nuclei does not change the affinity or maximum number of detectable in vitro d-[3H]LSD binding sites. The regional distribution in monkey brain of d-[3H]LSD binding and high affinity [3H]serotonin uptake, a marker for pre-synaptic serotonin nerve terminal density, shows some correlation. The most notable exceptions are cerebral cortical areas which are highest in d-[3H]LSD binding and only intermediate in [3H]serotonin uptake. Our evidence suggests that d-[3H]LSD binds to post-synaptic serotonin receptors.
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U2 - 10.1016/0006-8993(75)90234-6
DO - 10.1016/0006-8993(75)90234-6
M3 - Article
C2 - 239784
AN - SCOPUS:0016695856
SN - 0006-8993
VL - 94
SP - 523
EP - 544
JO - Brain research
JF - Brain research
IS - 3
ER -