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Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT3A(b)) expressed in Xenopus laevis oocytes

Mair, I D and Lambert, J J and Yang, J and Dempster, J and Peters, J A (1998) Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT3A(b)) expressed in Xenopus laevis oocytes. British Journal of Pharmacology, 124 (8). pp. 1667-74. ISSN 0007-1188

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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-HT3A(b)) heterologously expressed in Xenopus laevis oocytes. At negative holding potentials, bath applied 5-HT (300 nM - 10 microM) evoked a transient, concentration-dependent (EC50 = 1.1+/-0.1 microM), 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-HT3 receptor selective agonists 2-methyl-5-HT (EC50= 4.1+/-0.2 microM), 1-phenylbiguanide (EC50=3.0+/-0.1 microM), 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 microM) of 5-HT. 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 microM). The data are discussed in the context of results previously obtained with the human and mouse orthologues of the 5-HT3A 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-HT3A subunit orthologues.