Our aim is to classify and characterize peripheral effector receptors for 5-hydroxytryptamine (5-HT). A functional (pharmacological) approach to the problem is taken using isolated tissues set-up in vitro. Initial studies will be done on the isolated perfused rat kidney, the isolated rat vas deferens, and the isolated perfused rat mesenteric arteries. Subsequent experiments will be done with rat isolated atria, caudal arteries, and saphenous veins. The experiments will focus on peripheral receptors for 5-HT at sympathetic neuroeffector junctions at both prejunctional and postjunctional sites. Quantitative pharmacological analysis will be done with competitive antagonists, irreversible antagonists and a range of 5-HT-like agonists. The determination of pA2 values for competitive antagonists, agonist potency ratios, affinities and relative efficacies will be determined and used to classify and characterize the receptors. Criteria for defining three separate groups of 5-HT receptors (""""""""5-HT1-like"""""""", 5-HT2, and 5-HT3) are given and will serve as the broad basis for receptor classification. The project represents a careful basic science pharmacological research investigation into receptor classification and characterization. Such research is a prerequisite for the full understanding of the biological and pathological effects of 5-HT and for the rational development of new serotonergic drugs.
