Further characterization of 5-hydroxytryptamine receptors (putative 5-HT2B) in rat stomach fundus longitudinal muscle

摘要: 1. The present study was undertaken to isolate and characterize pharmacologically homogeneous populations of 5-hydroxytryptamine (5-HT) receptors from a possible mixed receptor population mediating concentration the longitudinal muscle rat stomach fundus. Our aim extend pharmacological characterization 5-HT2B which is reported be expressed in this preparation. 2. To minimize spontaneous activity any influence circular on contractile response, narrow (1-1.5 x 20 mm) segments mucosa-denuded were used. Under these conditions, blockade monoamine oxidase with pargyline (100 microM for 15 min) caused leftward displacement concentration-effect curves both 5-methoxytryptamine (5-MeO-T) tryptamine. Neither nor number uptake inhibitors affected responses 5-HT. 3. In pretreated preparations, order potency tryptamine analogues as follows: 5-MeO-T > or = alpha-Me-5-HT 5-HT 5-carboxamidotryptamine (5-CT) 2-Me-5-HT. addition several ligands known act agonists at either 5-HT2A 5-HT2C including 1-m-chlorophenylpiperazine (m-CPP), Ru 24969, MK 212 SCH 23390 also fundus whilst sumatriptan, renzapride 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) very weak inactive. With exception 2-Me-5-HT m-CPP, most produced monophasic consistent an interaction single site. High concentrations evoked relaxations blocked by phentolamine (1 MicroM) suggesting alpha-adrenoceptors. m-CPP often biphasic second phase insensitive yohimbine higher than required antagonism 5-HT.4. LY 53857, methiothepin, methysergide, ritanserin ICI 170809 potent but non-surmountable antagonists contrast, behaved surmountable following potency: rauwolscine >yohimbine mesulergine mianserin SB 204070 >WY 26703 200646> pirenpirone> renzapride. DAU 6285, granisetron, spiperone, ketanserin,phentolamine GR 127935 did not affect up 1 pM. agonist independent profile supported site antagonists.5. We conclude that despite small differences concerning enantiomeric selectivity affinity yohimbine, close identity recently cloned maintained. 200646, demonstrates some fundus, should provide useful ligand confirmation view allow discrimination function vitro vivo.