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Drummond AH, Bucher F, Levitan IB.
“LSD Labels a Novel Dopamine Receptor in Molluscan Nervous System”.
Nature. 1978;272(5651):368-70.
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Abstract
The binding of LSD to a dopamine receptor in the molluscan nervous system is reported. A particulate fraction from the circumesophageal ring of ganglia comprising the CNS of the Roman snail Helix pomatia was used for binding studies. Various putative neurotransmitters were tested for their ability to decrease specific (3H)-LSD binding using 1 nM (3H)-LSD. Only dopamine and (serotonin) 5-HT (>/= 10 mcM) were effective inhibitors but noradrenaline, octopamine and histamine were inactive. The effects of dopamine and 5-HT were additive at concentrations below 100 mcM. At higher concentrations (500 mcM), binding was abolished by either agent acting alone. To discriminate between the dopamine-sensitive site (D-site) and the 5-HT-sensitive site (S-site) experiments were performed to find a concentration of 5-HT which would abolish binding of (3H)-LSD to the S-site, without affecting binding to the D-site. (3H)-LSD binding displaced by 10 4 M 5HT was insensitive to dopamine and vice-versa. In a preliminary pharmacological investigation of the D-site, Epinine (N-methyldopamine) and dopamine were the most potent of the catecholamines tested as competitors of dopamine-sensitive (3H)-LSD binding. 1-Noradrenaline, 1-isoproterenol and 13-phenethylamine were much less active than epinine. (3,4-Dibydroxyphenylamino)-Z-imidazoline (DPI) was a potent inhibitor of dopamine sensitive (3H)-LSD binding. With the exception of most 5-substituted compounds, tryptamine derivatives (N - methyltryptamine, bufotenine, 6 , 7 - dibydr oxytryptamine, tryptamine, 6 -hydroxytryptamine, 5 -methoxytryptamine, N-methyl 5-hydroxytryptamine, 5,6-dihydroxytryptamine and 5-hydroxytryptamine) were effective inhibitors of binding. Ergot alkaloids and derivatives (d-l-LSD, ergotamine, ergometrine, dihydroergocryptine and methysergide) were very potent inhibitors. Neuroleptics (d and 1-butaclamol, chlorpromazine, cis- and trans-chlorprothixene, spiroperidol, haloperidol, cis, and trans- flupenthixol and pipamperone) were much less effective. Only d-butaclamol was a stereospecific inhibitor of (3H)-LSD binding in snail brain. (3H)-LSD labels the dopamine receptor which mediates a hyperpolarizing response in molluscan neurones.
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