Summary, Thoughts, and Future Perspectives

As all of the chapters in this book demonstrate, there has been much recent progress in the tachykinin receptor field and many exciting scientific discoveries have appeared. The report by Masu et al. in 1987 of the structure of the bovine stomach NIS receptor marked the first neuropeptide receptor of any kind to have its primary structure determined. Since then, many other neuropeptide receptor structures have been reported, including what seem to be mammalian NK2 and NK3 receptors (Nakanishi, 1991). It is not surprising that these tachykinin receptor types are all G-protein-linked since the natural agonists of these receptors have long been known to be efficient stimulators of phosphatidylinositol hydrolysis in the appropriate tissues. The regulation of the expression of these tachykinin receptors can now be studied, and hopefully this will provide some explanation of the peptide-receptor mismatch that has been discussed in this volume. And, it should now be possible to address the issue of potential receptor subtypes and whether there are just NK1, NK2, and NK3 receptors or if the tachykinin receptor story is even more complicated. The growing application of computerized tachykinin receptor structure analysis, coupled with the production of mutant receptors for biological analysis, will no doubt hasten our understanding of all of the tachykinin receptors and allow for the design and development of specific ligands for each receptor type. Of course, this progress will be aided by the similarity in receptor structure and function of the tachykinin receptors to other G-protein-linked receptors, both peptidergic and nonpeptidergic.