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

Abstract

1. The effects of 5-HT3 selective agonists have been studied in whole-cell voltage-clamped N1E-115 neuroblastoma cells. 2. 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. 3. 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. 4. In the presence of 100 microM 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. 5. 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). 6. 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.

• Authors: M I Sepúlveda, S C Lummis, I L Martin
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 104 Issue 2 Pg. 536-40 (Oct 1991) ISSN: 0007-1188 [Print] England
• PMID: 1797317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biguanides
• Receptors, Serotonin
• Serotonin
• 2-methyl-5-HT
• 1-(3-chlorophenyl)biguanide

Topics

• Animals
• Biguanides (pharmacology)
• Membrane Potentials (drug effects)
• Mice
• Neuroblastoma (pathology)
• Neurons (drug effects)
• Radioligand Assay
• Receptors, Serotonin (drug effects)
• Serotonin (analogs & derivatives, pharmacology)
• Tumor Cells, Cultured