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 investigated in the intestinal tract and the striatum in guinea-pig, in binding studies using the 5-HT4 radioligand, [3H]GR113808. In the intestinal tract, specific binding was observed in preparations of the longitudinal muscle with the myenteric plexus (LMMPs) but not in the whole tissue. Saturable binding of [3H]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 protein). Selective 5-HT4 receptor agonists and antagonists inhibited binding of [3H]GR113808 with high affinities in LMMPs of the ilcum and which correlated well with their actions on the striatum (r = 0.98), as indicated by the rank order of displacement potencies: SDZ205-557 > LY297524 > cisapride = BIMU8 > 5-HT > mosapride > renzapride > 5-hydroxy-N-methyltryptamine(5-HMT) > (+/-) zacopride > alpha-methyl-5-hydroxytryptamine (alpha-M-5-HT) > 5-methyltryptamine(5-MT) > 5-carboxamidotryptamine (5-CT). The number of binding sites of [3H]GR113808 in the intestine was significantly smaller than that in the brain. In the intestine, a larger number of binding sites was noted in the upper part of the intestine, the rank order being duodenum > jcjunum > ilcum > > colon > rectum. Such data are relevant regarding the potential use of the 5-HT4 receptor ligand to modify motility and secretion in the intestine.
Uchiyama-Tsuyuki
Y
Y
OTC Pharmacology Laboratory, OTC Product R&D Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Saitoh
M
M
Muramatsu
M
M
D000818:Animals; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000378:metabolism*; D006168:Guinea Pigs; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D014316:Tritium; D044422:Receptors, Serotonin, 5-HT4; C082871:GR 113808