Characterisation of 5-HT₂ receptor subtypes in the Suncus murinus intestine

The involvement of 5-HT₂ receptor subtypes in mediating a contraction response in the isolated intestine of Suncus murinus was investigated using DOI ((±)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane, a 5-HT₂ receptor agonist) which produced a bell-shaped concentration response curve that was significantly (p<0.05) reduced by methysergide (a 5-HT(1/2) receptor antagonist, 1 μM) but not ketanserin (a 5-HT(2A) receptor antagonist, 1 μM), yohimbine (a 5-HT(2B) receptor antagonist, 1 μM) or a combination of ondansetron (a 5-HT₃ receptor antagonist, 1 μM) plus SB204070 (8-amino-7- chloro(N-butyl-4-piperidyl) methylbenzo-1,4-dioxan-5-carboxylate hydrochloride, a 5-HT₄ receptor antagonist, 1 nM). The contraction response to the lower concentrations of DOI (10 nM-0.3 μM) was reduced in the presence of SB206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5- tetrahydropyrrolo[2,3-f]indole, a 5-HT(2B/2C) receptor antagonist, 1 μM), whilst conversely, the reducing response to the higher concentrations of DOI (1-30 μM) was prevented. A repeated challenge with 3 μM DOI produced a smaller response (desensitisation) and also reduced the response to 5-HT (5- hydroxytryptamine, 0.3 μM) that was inhibited by SB206553 (1 μM). Data indicate that 5-HT(2C) receptors are likely candidates to mediate the contractile response to DOI and demonstrate desensitisation to repeated challenges.