5-HT4 Receptors in Lower Urinary Tract Tissues

Interest in the role of 5-HT in the physiology and pathophysiology of the lower urinary tract (LUT), and its effect on neurotransmission in the bladder and urethra, has developed considerably over the last 20 years,1,2 reflecting the increased awareness of therapeutic potential and the relative inadequacy of current therapies for LUT disorders. 5-HT is recognized now as an ubiquitous intercellular signaling molecule. A great diversity of cell types can synthesize, store, release, uptake, as well as respond to extracellular 5-HT. This, coupled with the tremendous number and diversity of receptor proteins, implicates 5-HT in many physiological and pathophysiological processes. The importance of 5-HT in the regulation of the behavior of the “hollow organs” (e.g., discrete parts of the alimentary tract, the heart, the vasculature, and the bladder) has been well established.3–5 It is now clear that the many receptors for 5-HT (at least 14 known subtypes) allow for so many forms of modulation that tremendous subtleties in organ function can be introduced by selective receptor subtype activation or antagonism. Largely because 5-HT functions as a modulatory, rather than direct, transmitter in so many organs, the attractiveness of selective interaction with 5-HT receptors is great. Clearly, the opportunities for new, selective disease therapies are tremendous, and diseases of the LUT, which are poorly served by current drugs, are a key area for advancement in an ever-aging population.