[125I]S(-)-zacopride labels a novel 5-hydroxytryptamine sensitive recognition site in rat duodenum and ileum.
Autoradiographic binding studies using [125I]S(-)-zacopride (0.1 nM) identified non-5-HT3 specific binding sites (defined by 5-hydroxytryptamine (5-HT), 1.0 microM) in the rat duodenum and ileum and some other peripheral tissues (adrenal gland, liver, stomach, kidney and spleen). In the rat duodenum and ileum, saturation studies with [125I]S(-)-zacopride indicated that the specific binding was saturable and of high affinity to an apparently homogenous population of binding sites (duodenum Bmax = 1.88 fmol/mg, Kd = 0.078 nM; ileum Bmax = 1.60 fmol/mg, Kd = 0.071 nM). Competition studies with slices of either duodenum or ileum indicated that the pharmacology of the [125I]S(-)-zacopride recognition site in both tissues was comparable but differed from all 5-HT receptors and uptake sites reported to date. However, the [125I]S(-)-zacopride recognition site displayed some pharmacological and regional similarity to the 5-HT1P recognition site: The sensitivity of the [125I]S(-)-zacopride binding in the duodenum and ileum to GTP indicates that the radiolabelled recognition site may represent a functional G-protein coupled receptor.
Ge
J
J
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, UK.
Towers
P
P
Patel
A C
AC
Barnes
N M
NM
D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism* / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007082:Ileum / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000378:metabolism* / Q000494:pharmacology
D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012702:Serotonin Antagonists; D006160:Guanosine Triphosphate; C055971:zacopride