The binding characteristics of a radiolabelled 5-HT3receptor agonist, [3H]meta-chlorophenylbiguanide (mCPBG), were examined in membranes from N1E-115 neuroblastoma cells. Scatchard plots of saturation binding data showed the presence of two populations of binding sites, with Kd= 0.03 ± 0.01 nM and 4.4 ± 1.2 nM and Bmax= 11.9 ± 4.2 and 897.9 ± 184.7 fmol/mg protein respectively. Competition studies with a selection of agonists revealed the pharmacological profile expected for a 5-HT3receptor. The rank order of potency for antagonists was granisetron >quipazine >GR65630 >ondansetron >MDL72222, and for agonists was mCPBG >5-HT (5-hydroxytryptamine, serotonin) >2-methyl-5-HT. IC50values for 5-HT and 2-methyl-5-HT were lower than those observed using radiolabelled antagonists, and combined with functional experiments, the data suggest that [3H]mCPBG may label high affinity desensitized states of the receptor. We conclude that [3H]mCPBG labels 5-HT3receptors in N1E-115 neuroblastoma cell membranes and may be a useful compound with which to explore 5-HT3receptors in other systems. © 1993.
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