5-Hydroxytryptamine receptors in vertebrates and invertebrates: why are there so many?

In the accompanying review article, Saudou and Hen provide a comprehensive review of 5-hydroxytryptamine (5-HT) receptors. The authors appropriately raise the question of "why are there so many 5-HT receptors"? They suggest briefly that receptor multiplicity allows 5-HT to have diverse effects in the nervous system. However, 5-HT receptor multiplicity exceeds that of other biogenic amine receptors so that other explanations might be added to their suggestion. Recently, it has been hypothesized that G protein-coupled 5-HT receptors have existed for more than 750 million years (Peroutka and Howell, 1994). Although a recent flurry of "new" 5-HT receptors have appeared in the literature, the "primordial" 5-HT receptor appears to have appeared prior to the evolution of muscarinic, dopaminergic and adrenergic receptor systems. Therefore, the fact that the primordial 5-HT receptor evolved prior to other G protein-coupled biogenic amine receptors may be the reason that so many 5-HT receptors exist today.