IDENTIFICATION AND CHARACTERIZATION OF THE 5-HT4 RECEPTOR IN THE INTESTINAL-TRACT AND STRIATUM OF THE GUINEA-PIG

Receptors for 5-hydroxytryptamine (5-HT) of the 5-HT4 type were invest igated in the intestinal tract and the striatum in guinea-pig, in bind ing studies using the 5-HT4 radioligand, [H-3]GR113808. In the intesti nal tract, specific binding was observed in preparations of the longit udinal muscle with the myenteric plexus (LMMPs) but not in the whole t issue. Saturable binding of [H-3]GR113808 was demonstrated (striatum: Kd = 0.054 +/- 0.002 nM, Bmax = 90.25 +/- 10.44 fmol/mg protein, LMMPs of ileum: Kd = 0.077 +/- 0.016 nM, Bmax = 11.95 +/- 3.24 fmol/mg prot ein). Selective 5-HT4 receptor agonists and antagonists inhibited bind ing of [H-3]GR113808 with high affinities in LMMPs of the ileum and wh ich correlated well with their actions on the striatum (r = 0.98), as indicated by the rank order of displacement potencies: SDZ205-557 > LY 297524 > cisapride = BIMU8 > 5-HT > mosapride > renzapride > 5-hydroxy -N-methyltryptamine(5-HMT) > (+/-)zacopridc > alpha-methyl-5-hydroxytr yptamine (alpha-M-5-HT) > 5-methyltryptamine(5-MT) > 5-carboxamidotryp tamine (5-CT). The number of binding sites of [H-3]GR113808 in the int estine was significantly smaller than that in the brain. In the intest ine, a larger number of binding sites was noted in the upper part of t he intestine, the rank order being duodenum > jejunum > ileum much gre ater than colon > rectum. Such data are relevant regarding the potenti al use of the 5-HT4 receptor ligand to modify motility and secretion i n the intestine.