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SEROTONIN BINDING PROTEIN: ENHANCEMENT OF BINDING BY Fe 2+ AND INHIBITION OF BINDING BY DRUGS 1 2
Author(s) -
Tamir Hadassah,
Klein Athalia,
Rapport Maurice M.
Publication year - 1976
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1976.tb06467.x
Subject(s) - serotonin , chemistry , reserpine , binding site , serotonergic , imipramine , biophysics , stereochemistry , biochemistry , pharmacology , receptor , biology , medicine , alternative medicine , pathology
— The binding of serotonin to a soluble, high affinity binding protein, present in synaptosomes and associated with serotonergic tracts, has now been studied for the effects of metallic ions and various drugs. At optimal concentration (10 ‐4 M) of Fe 2+ the enhancement of binding was close to 20‐fold. A much smaller effect was noted with Cu 2+ . With other ions (Fe 3+ , Mn 2+ , Co 2+ , Ni 2+ , Cr 3+ , Mg 2+ , Ca 2+ ) little or no effect was seen. For the effect with Fe 2+ . preincubation was required (10 min, 25°C) and concentrations higher than 10 ‐4 M were inhibitory. Studies based on equilibrium dialysis show that the effect of Fe 2+ was on the affinity of the binding of serotonin to the protein, rather than on the binding capacity. In polydcrylamide gels at pH 8.6 the migratory properties of thc serotonin‐protein complex formed in the presence of Fe 2+ differ from those of the complex formed without Fe 2+ . Nucleotides (ATP, GTP, ADP, AMP) inhibited thc binding. The effects of several classes of drugs (inhibitors of biogenic amine storage and uptake, psychotomimetics, MAO) inhibitors and drugs binding to contractile proteins) were also studied. The only effective inhibitors of serotonin binding were reserpine, vinblastine and CZ‐74, which caused 50% inhibition at 2 × 10 ‐6 M, 7.5 × 10 ‐6 M and 0.2 × 10 ‐6 M respectively.