Bioassays for NPY receptors: old and new

Classical pharmacology performed on isolated organ preparations is an essential tool for receptor characterization and classification. Basic pharmacological parameters (e.g. ED50, ID50, pD2, pA2 as measures of apparent affinities) obtained by relating the agent concentration with the biological effect are the final results of the various steps required for drug action and necessarily reflect the complex mechanisms of cell function. Results obtained with bioassays are therefore a useful and essential part in the assessment of endogenous systems, in the present case, the NPY family of peptides and their receptors. An attempt has been made, in the present review, to present a choice of isolated organs that may provide a starting point towards the construction of a solid classical pharmacology of receptors for NPY and congeners. Some of these organs appear to be 'monoreceptor systems' (e.g. the rabbit saphenous vein) whose response is contributed by a single receptor type, others (e.g. the rat colon) are 'multiple receptor systems' and their pharmacology is much too complex and requires the use of a variety of compounds from the naturally occuring peptides, to some selective agonists and when available, specific and selective antagonists. Such compounds have been utilised by us and other workers to detect specific biological responses to NPY and congeners in peripheral tissues: such responses have been quantified, carefully analysed in pharmacological terms and characterized as biological effects mediated by Y1 (the rabbit saphenous vein), Y2 (dog saphenous vein, rat vas deferens, rat colon), Y4 (rat colon) and Y5 (rabbit ileum) receptors. Compared to findings obtained with binding assays and molecular biology experiments, the results of the bioassays show very interesting similarities. Much remains however to be done in view of providing the classical pharmacological bases that are needed in the field of NPY.