Possible role of gangliosides in regulating an adenylate cyclase-linked 5-hydroxytryptamine (5-HT1) receptor.
Cultured NCB-20 hybrid cells express adenylate cyclase-coupled receptors for 5-hydroxytryptamine (5-HT) that correspond biochemically and pharmacologically to 5-HT1 receptors in rodent brain membrane preparations, apart from a much-reduced affinity for 5-HT (160 nM compared to less than 5 nM 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-HT1 receptor for 5-HT were tested. Both GM1 ganglioside (the cholera toxin receptor) and tetrasialoganglioside GQ1b produced a 10-fold increase in receptor affinity for [3H]5-HT, measured by binding studies. All gangliosides, at submicromolar concentrations, resulted in significantly reduced EC50 values for 5-HT-mediated elevation of intracellular cyclic AMP levels. GQ1b 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-HT1 receptor and the coupling of the 5-HT1 receptor-guanine nucleotide binding protein adenylate cyclase complex.
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology; D001923:Brain Chemistry; D002460:Cell Line; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000502:physiology; D005678:G(M2) Ganglioside / Q000502:physiology; D005732:Gangliosides / Q000502:physiology*; D006822:Hybrid Cells; D051379:Mice; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology
D005732:Gangliosides; D011985:Receptors, Serotonin; D005678:G(M2) Ganglioside; D012701:Serotonin; D005677:G(M1) Ganglioside; D000242:Cyclic AMP; D000262:Adenylyl Cyclases