Physiological functions and pharmacological targeting of transient receptor potential channels

Transient receptor potential (TRP) channels represent an extensive and diverse protein family fulfilling salient roles as versatile cellular sensors and effectors. The pivotal role of TRP and related ion channels in sensory processes has been well documented. Over the last few years, a new concept has emerged that TRP proteins control an exceptionally broad spectrum of homeostatic physiological functions such as maintenance of body temperature, blood pressure, transmitter release from neurons, mineral and energy homeostasis, and reproduction. This notion is further supported by more than 20 hereditary human diseases in areas as diverse as neurology, cardiology, hematology, pulmonology, nephrology, dermatology, and urology. Most TRP channel-related human disorders impinge on development, metabolism, and other homeostatic functions. The remarkable diversity of pathologies caused by TRP channel dysfunction underscores these proteins' broad spectrum of roles in vivo. Here, we provide a comprehensive overview of our progress in the identification, characterization, and clinical relevance of pharmacological agents targeting mammalian TRP channels. SIGNIFICANCE STATEMENT: Accumulating evidence links transient receptor potential (TRP) channels to various human diseases and highlights TRPs as the most appealing pharmacological targets. The review provides an overview of this quickly developing research area, focusing on identified pharmacological modulators of mammalian TRP channels.