Pharmacological characterization of a rat 5‐hydroxytryptamine type 3 receptor subunit (r5‐HT 3A(b) ) expressed in Xenopus laevis oocytes

The present study has utilized the two electrode voltage‐clamp technique to examine the pharmacological profile of a splice variant of the rat orthologue of the 5‐hydroxytryptamine type 3A subunit (5‐HT 3A(b) ) heterologously expressed in Xenopus laevis oocytes. At negative holding potentials, bath applied 5‐HT (300 n M –10 μ M ) evoked a transient, concentration‐dependent (EC 50 =1.1±0.1 μ M ), inward current. The response reversed in sign at a holding potential of −2.1±1.6 mV. The response to 5‐HT was mimicked by the 5‐HT 3 receptor selective agonists 2‐methyl‐5‐HT (EC 50 =4.1±0.2 μ M ), 1‐phenylbiguanide (EC 50 =3.0±0.1 μ M ), 3‐chlorophenylbiguanide (EC 50 =140± 10 n M ), 3,5‐dichlorophenylbiguanide (EC 50 =14.5±0.4 n M ) and 2,5‐dichlorophenylbiguanide (EC 50 = 10.2±0.6 n M ). With the exception of 2‐methyl‐5‐HT, all of the agonists tested elicited maximal current responses comparable to those produced by a saturating concentration (10 μ M ) of 5‐HT. Responses evoked by 5‐HT at EC 50 were blocked by the 5‐HT 3 receptor selective antagonist ondansetron (IC 50 =231±22 pM) and by the less selective agents (+)‐tubocurarine (IC 50 =31.9± 0.01 n M ) and cocaine (IC 50 =2.1±0.2 μ M ). The data are discussed in the context of results previously obtained with the human and mouse orthologues of the 5‐HT 3A subunit. Overall, the study reinforces the conclusion that species differences detected for native 5‐HT 3 receptors extend to, and appear largely explained by, differences in the properties of homo‐oligomeric receptors formed from 5‐HT 3A subunit orthologues.British Journal of Pharmacology (1998) 124 , 1667–1674; doi: 10.1038/sj.bjp.0702037