Serotonin Receptor Subtypes in Brain: Ligand Binding Properties and Coupling with G Proteins
Serotonin (5-hydroxytryptamine; 5-HT) receptors are classified as 5-HT1, 5-HT2 and 5-HT3, and evidence is emerging to suggest heterogeneity within 5-HT1 receptor category, e.g., 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors (Peroutka, 1988). Several GTP-binding proteins (G proteins) in mammalian brain were identified, e.g., α52/45, α41, α40, α39 (α-subunits of Gs, Gi1, Gi2 and Go) (Katada et al., 1986a; Katada et al., 1987; Itoh et al., 1988; Casey and Gliman, 1988) and several G proteins with low molecular weight (20 ~ 30 kDa), including 24-kDa G protein (24 K-G) (Katada and Ui, 1988), ADP-ribosylation factor (ARF) (Kahn and Gliman, 1986), a substrate of botulinum toxin (Gb, rho product) (Narumiya et al., 1988) and other small molecular G proteins (smg) (Takai et al., 1989). N-ethylmaleimide (NEM) has been used as a useful probe to alkylate sulfhydryl residues in receptors and G proteins involved in their coupling (Katada et al., 1986b; Kitamura and Nomura, 1987; Nomura et al., 1988). To classify 5-HT receptor subtypes in the CNS from binding characteristics and the aspect of coupling properties of these receptors with G proteins, we here examined the effects of GTPyS, NEM and several 5-HT receptor ligands on specific binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-HT1A), [125I]iodocyanopindolol (ICYP) (5-HT1B), [ 3H]mesulergine (5-HT1C), [3H] 4-bromo-2,5-dimethoxyphenyliso-propylamine (DOB) (5-HT2) and [3H]ketanserin (5-HT2) to crude synaptic membranes of rat brain.
KeywordsPertussis Toxin Brain Membrane Competition Curve Guanine Nucleotide Regulatory Protein Receptor Clone
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