[I-125] S(-)-ZACOPLIDE LABELS A NOVEL 5-HYDROXYTRYPTAMINE SENSITIVE RECOGNITION SITE IN RAT DUODENUM AND ILEUM

Autoradiographic binding studies using [I-125]S(-)-zacopride (0.1 nM) identified non-5-HT3 specific binding sites (defined by 5-hydroxytrypt amine (5-HT), 1.0 mu M) in the rat duodenum and ileum and some other p eripheral tissues (adrenal gland, liver, stomach, kidney and spleen). In the rat duodenum and ileum, saturation studies with [I-125]S(-)-zac opride indicated that the specific binding was saturable and of high a ffinity to an apparently homogenous population of binding sites (duode num, B-max - 1.88 fmol/mg, K-d = 0.078 nM; ileum, B-max = 1.60 fmol/mg , K-d = 0.071 nM), Competition studies with slices of either duodenum or ileum indicated that the pharmacology of the [I-125]S(-)-zacopride recognition site in both tissues was comparable but differed from all 5-HT receptors and uptake sites reported to date. However, the [I-125] S(-)-zacopride recognition site displayed some pharmacological and reg ional similarity to the 5-HT1P recognition site. The sensitivity of th e [I-125]S(-)-zacopride binding in the duodenum and ileum to GTP indic ates that the radiolabelled recognition site may represent a functiona l G-protein coupled receptor.