Trends in Pharmacological Sciences
Functional, molecular and pharmacological advances in 5-HT7 receptor research
Section snippets
Pharmacology and knockouts
The availability of selective ligands is of utmost importance to the elucidation of the characteristics and function of a receptor. However, a well-characterized selective agonist for the 5-HT7 receptor is not yet available. Furthermore, the fact that 8-OH-DPAT, previously considered to be the standard selective agonist for the 5-HT1A receptor, has high affinity for the 5-HT7 receptor adds to the confusion regarding which receptor subtype is involved in previously observed phenomena. Most
5-HT7 receptor signaling
Although coupling of the 5-HT7 receptor to cAMP formation has been known since the discovery of the receptor 3, 4, 5, recent studies have elucidated the functional coupling of the 5-HT7 receptor in more detail. At least when expressed in cell lines, the receptor is tightly associated with the G protein, regardless of agonist binding [21]. The receptor activates the extracellular signal-regulated kinase (ERK) through a mechanism that is dependent on a Ras monomeric GTPase [22]. Although ERK
Distribution of the 5-HT7 receptor
Early and more-recent studies in guinea-pigs and rats have used in situ hybridization to determine with increasing resolution where the gene encoding the 5-HT7 receptor is expressed 4, 25, 26, 27. The studies all show that 5-HT7 receptor mRNA is most abundant in the thalamus, hippocampus and hypothalamus. It is noteworthy that 5-HT7 receptor mRNA is present in all of the CA fields of the hippocampus and in the suprachiasmatic nucleus (SCN) of the hypothalamus. Mapping of the expression of the
Thermoregulation
The involvement of 5-HT in thermoregulation is a well-known phenomenon. For example, injection of 5-CT or 8-OH-DPAT induces hypothermia in rodents. The hypothermic effect is similar regardless of whether the drug is administered peripherally or centrally, suggesting a central mechanism of action. Because both 5-CT and 8-OH-DPAT are 5-HT1A receptor agonists, this receptor was generally considered to be the main mediator of the hypothermia, although some reports had suggested the involvement of
Concluding remarks
The availability of selective antagonists and knockout mice has led to an unprecedented activity in 5-HT7 receptor research. As a result, the distribution and functional coupling of the receptor has been determined in more detail and many important roles for the receptor have been identified in thermoregulation, learning and memory, hippocampal activity, endocrine function, sleep, circadian rhythms and mood. Future studies and pharmaceutical development should determine whether a 5-HT7 receptor
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