Pharmacological characterization of a rat 5-hydroxytryptamine type₃ receptor subunit (r5-HT(3A(b)) expressed in Xenopus laevis oocytes

1. 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. 2. at negative holding potentials, bath applied 5-HT (300 nM-10 μM) evoked a transient, concentration-dependent (EC₅₀ = 1.1 ± 0.1 μM). inward current. The response reversed in sign at a holding potential of -2.1 ± 1.6 mV. 3. The response to 5-HT was mimicked by the 5-HT, receptor selective agonists 2-methyl-5-HT (EC₅₀ = 4.1 ± 0.2 μM), 1-phenylbiguanide (EC₅₀ = 3.0 ± 0.1 μM), 3-chlorophenylbiguanide (EC₅₀ = 140 ± 10 nM, 3,5-dichlorophenylbiguanide (EC₅₀ = 14.5 ± 0.4 nM) and 2,5-dichlorophenylbiguanide (EC₅₀ = 10.2 ± 0.6 nM). 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 μM) of 5-HT. 4. Responses evoked by 5-HT at EC₅₀ were blocked by the 5-HT₃ receptor selective antagonist ondansetron (IC₅₀ = 231 ± 22 pM) and by the less selective agents (+)-tubocurarine (IC₅₀ = 31.9 ± 0.01 nM) and cocaine (IC₅₀ = 2.1 ± 0.2 μM). 5. 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-HT₃ receptors extend to, and appear largely explained by, differences in the properties of homo-oligomeric receptors formed from 5-HT(3A) subunit orthologues.