The agonist properties of m‐chlorophenylbiguanide and 2‐methyl‐5‐hydroxytryptamine on 5‐HT3 receptors in N1E‐115 neuroblastoma cells

Abstract

The effects of 5‐HT3 selective agonists have been studied in whole‐cell voltage‐clamped N1E‐115 neuroblastoma cells. Application of 5‐hydroxytryptamine (5‐HT) results in the rapid development of a transient inward current at quasiphysiological membrane potentials. This current can be blocked by the 5‐HT3 specific antagonists BRL 43694 and GR67330. Application of 2‐methyl‐5‐HT (2‐Me5‐HT), a 5‐HT3 selective agonist, produced a qualitatively similar inward current, but with a maximum response only 20% of that produced by 5‐HT. In the presence of 100 μm 2‐Me5‐HT, the upper part of the 5‐HT dose‐response curve was shifted to the right but reached the same maximum value as in the absence of 2‐Me5‐HT. 2‐Me5‐HT appears therefore to be a partial agonist under these conditions. The novel 5‐HT3 agonist, meta‐chlorophenylbiguanide (mCPBG) is a full agonist, but has a Hill coefficient (1.5) significantly less than that of 5‐HT (2.3). Comparison with radioligand binding data show that mCBPG is 100 times less potent than expected; it may therefore exhibit a high affinity for a desensitized state. 1991 British Pharmacological Society