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Possible Role of Gangliosides in Regulating an Adenylate Cyclase‐Linked 5‐Hydroxytryptamine (5‐HT 1 ) Receptor
Author(s) -
BerryKravis Elizabeth,
Dawson Glyn
Publication year - 1985
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.1471-4159.1985.tb10529.x
Subject(s) - adenylate kinase , receptor , cyclase , cholera toxin , 5 ht receptor , ganglioside , chemistry , biochemistry , potency , g protein , biology , medicine , endocrinology , serotonin , in vitro
Cultured NCB‐20 hybrid cells express adenylate cyclase‐coupled receptors for 5‐hydroxytryptamine (5‐HT) that correspond biochemically and pharmacologically to 5‐HT 1 receptors in rodent brain membrane preparations, apart from a much‐reduced affinity for 5‐HT (160 n M compared to < 5 n M in brain). Since NCB‐20 cells also differ from rodent brain both qualitatively and quantitatively in their ganglioside composition, the effects of exogenously added gangliosides on the affinity of the 5‐HT 1 receptor for 5‐HT were tested. Both G M1 ganglioside (the cholera toxin receptor) and tetrasialoganglioside G Q1b produced a 10‐fold increase in receptor affinity for [ 3 H]5‐HT, measured by binding studies. All gangliosides, at submicromolar concentrations, resulted in significantly reduced EC 50 values for 5‐HT‐mediated elevation of intracellular cyclic AMP levels. G Q1b had the capacity to most dramatically enhance the potency of 5‐HT in mediating increases in cyclic AMP levels. Gangliosides had no effect on the potency of DADLE or 3,4‐dihydroxyphenylethylamine (dopamine)‐mediated depression of cyclic AMP levels, suggesting some specificity for 5‐HT. Our data are interpreted as implying a specific role for polysialogangliosides in modulating the affinity of the 5‐HT 1 receptor and the coupling of the 5‐HT 1 receptor‐guanine nucleotide binding protein adenylate cyclase complex.