PHARMACOLOGICAL CHARACTERIZATION OF A 5-HT RECEPTOR IN LOCUST NERVOUS-TISSUE

A 5-HT receptor in the nervous tissue of the desert locust (Schistocerca gregaria Forsk.) was investigated, using [H-3]LSD (lysergic acid diethylamide) as the radioligand. [H-3]LSD labels in addition a putative dopamine receptor whose specific [H-3]LSD binding nevertheless could easily be diminished by co-incubation with 1 muM dopamine. The binding site was characterized by a K(D) of 1.64 nM, and a maximal concentration of binding sites of 79.8 fmol/mg protein. Pharmacological investigation revealed a relatively low affinity for the putative natural agonist, serotonin (K(I) = 0.209 muM). In contrast to the high affinity of classical serotonergic antagonists (e.g. dihydroergotamine or (+)-butaclamol) substances with subtype specificity such as 8-OH-DPAT (8-hydroxy-1-(N,N-dipropyl)-aminotetralin) or ketanserin have only moderate affinities. Quantitative comparison of the pharmacological data demonstrated that there is obviously no pharmacological homology with vertebrate 5-HT receptors characterized so far. The only receptors with a close pharmacological relationship to the 5-HT receptor of locusts are the 5-HT(drol) receptor expressed in Drosophila nervous tissue and a 5-HT receptor in snail nervous tissue which might be homologous to that of locusts. The 5-HT receptor investigated, was shown to be G-protein-coupled, as addition of stable GTP analogues or depletion of Mg2+ ions from the incubation medium led to agonist-specific lowering of the affinity.