Biochemical and Biophysical Research Communications, Vol.508, No.2, 590-596, 2019
SR 57227A is a partial agonist/partial antagonist of 5-HT3 receptor and inhibits subsequent 5-HT- or SR 57227A-induced 5-HT3 receptor current
The serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptors are transmembrane ligand-gated ion channels. Although several 5-HT3 receptor agonists have been used as preclinical tools, SR 57227A is the most commonly used 5-HT3 receptor agonist with the ability to cross the blood brain barrier. However, the precise pharmacological profile of SR 57227A remains unclear. Therefore, we examined the pharmacological profile of SR 57227A at the 5-HT(3)A and 5-HT(3)AB receptors. We microinjected Xenopus laevis oocytes with human 5-HT(3)A complementary RNA (cRNA) or a combination of human 5-HT(3)A and human 5-HT(3)AB cRNA and performed two electrode voltage clamp recordings of 5-HT(3)A and 5-HT(3)AB receptor current in the presence of SR 57227A. Results showed that SR 57227A acts as partial agonist/partial antagonist at the 5-HT3 receptor. Interestingly, SR 57227A specifically reduced subsequent current amplitudes induced by 5-I-IT or SR 57227A. Based on its 5-HT3 receptor partial agonist/partial antagonist properties, we predict that SR 57227A functions as a serotonin stabilizer. (C) 2018 Elsevier Inc. All rights reserved.