Central and peripheral 5-HT receptors in the leech (Hirudo medicinalis) redefined

1. 5-Hydroxytryptamine (5-HT) receptors in the Retzius neurones (R cells) and longitudinal body wall muscle strips of the leech H. medicinalis were studied using a range of selective agonists developed for mammalian receptors. 2. All agonists induced hyperpolarisation of R cells: the order of their potency was 5-HT > 5-CT > 2-Me 5HT > alpha-Me-5-HT > > CGS-12066B = 5MeOT > PAPP > Buspirone. This receptor is most like a mammalian 5-HT1C/2 receptor. 3. 5-HT induces relaxation of body wall strips, preceded at higher doses by contraction or an increase in spontaneous contractions. The relaxing effect was best mimicked by 5-CT and alpha-Me-5-HT, suggesting a 5-HT1C/2 receptor. The contractile effect was best mimicked by 5-MeOT suggesting a 5-HT4-like receptor. The overall potency of agonists on the body wall muscle was 5-MeOT > 5-CT > 5-HT > alpha-Me-5-HT > 2-Me 5-HT > PAPP > Buspirone > > CGS-12066B. 4. Results suggest that either the sites of 5-HT action possess several different receptors or the receptors themselves are more complex with multiple properties.