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Second Messengers in the Definition of 5-HT Receptors

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Book cover Serotonin: Molecular Biology, Receptors and Functional Effects

Summary

Radioligand binding studies have been instrumental in the discovery of 5-HT receptor subtypes, but have clear limitations. By contrast, second messenger studies are elegant tools, although somewhat overlooked for classifying functional receptors. In the particular case of 5-HT1 receptor subtypes, few “classical” isolated tissue preparations have been described, whereas second messenger systems are available. 5-HT1A, 5-HT1B and 5-HT1D receptors are negatively coupled to adenylate cyclase, whereas 5-HT1C, receptors (like 5-HT2 receptors) stimulate phospholipase C. The rank orders of potency of agonists and antagonists established in second messenger studies correlated significantly with rank orders of affinity determined in specific radioligand binding assays. Subsequently, a variety of functional 5-HT1C receptor subtypes-mediated effects have been described in both the CNS and periphery. The profile established for 5-HT1C receptor-mediated stimulation of phospholipase C will be especially useful in the definition of functional 5-HT1C receptors, although 5-HT1C and 5-HT2 receptors have similar pharmacological profiles and second messenger systems. 5-HT3 receptors form ligand gated channels and thus, do not directly activate second messenger systems. Even more interesting is the case of the 5-HT4 receptor which stimulates adenylate cyclase in colicullus cell cultures, and for which no binding site has been as yet described. Second messenger studies have permitted the identification of similar functional receptors in various peripheral models, and have contributed significantly to the definition of new functional 5-HT receptor subtypes.

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  1. Preclinical Research, Sandoz Pharma Ltd, CH-4002, Basel, Switzerland

    D. Hoyer, H. Boddeke & P. Schoeffter

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  2. H. Boddeke
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  1. Preclinical Research, Sandoz Pharma Ltd., P.O. Box 6, CH-4002, Basel, Switzerland

    John R. Fozard

  2. Institute of Pharmacology, Erasmus University Rotterdam, P.O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands

    Pramod R. Saxena

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Hoyer, D., Boddeke, H., Schoeffter, P. (1991). Second Messengers in the Definition of 5-HT Receptors. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_11

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