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Hypoxic pulmonary vasoconstriction (HPV) is an essential physiological mechanism of the lung which matches perfusion to ventilation to optimize gas exchange. Pulmonary arterial smooth muscle cells (PASMC) are the effector and possibly also the sensor cells of HPV. Contraction of th ...

The airways of the lungs are composed of the epithelium, smooth muscle cells, and sensory nerve cells as well as resident immune cells. Transient receptor potential (TRP) channels are expressed in all of these tissues and cells and there is increasing evidence that they play a key role in respiratory ...

The transient receptor potential mucolipin (TRPML) subfamily of transient receptor potential cation channels consists of three members (TRPML1-3) that function at various stages of endocytosis. Conventional research in the TRPML field suggests that dysfunction along these e ...

The perception of temperature is critical in not only acute responses to changes in the environment but also fundamental in regulating homeostatic mechanisms like core body temperature. The somatosensory system detects changes in ambient temperature via the coordinated efforts ...

TRPM7 and its closely related protein TRPM6 are unique bifunctional molecules consisting of a kinase domain fused to an ion channel. The ion channel belongs to the transient receptor potential (TRP) family of ion channels, TRPM subfamily, while the kinase domain belongs to a family of atypical p ...

In this review we summarize the current data on the ion channels TRPM4 and TRPM5. These proteins are to date the only molecular candidates for the class of Ca2+-activated cation channels (CAN channels). They form monovalent cation-selective and Ca-impermeable ion channels, which are activa ...

The TRPM subfamily of transient receptor potential channels includes a number of members which are involved in cell proliferation or cell survival. TRPM2, the second member to be cloned, has a key role in the response to oxidative stress. After exposure to oxidant stress, TNFα, concanavalin A, or a ...

The physiological function of all cells is uniquely regulated by changes in cytosolic Ca2+ levels. Although several mechanisms increase cytosolic Ca2+ levels, Ca2+ influx across the plasma membrane upon the release of Ca2+ from the internal stores is one of the major mechanisms in most nonexc ...

TRPA1 is one of the few ion channels with human genetic validation for pain. A TRPA1 gain-of-function mutation is linked to familial episodic pain syndrome in humans. This milestone discovery, coupled with a growing preclinical literature implicating TRPA1 in multiple indications, has m ...

Transient receptor potential vanilloid 4 (TRPV4) was first identified in 2000 as an osmolarity sensor. Further investigations rapidly revealed this ion channel to be a polymodal receptor with additional activating or modulating stimuli including warm temperatures, endogeno ...

Following the discovery of transient receptor potential vanilloid 1 (TRPV1), the founding member of the subfamily, knowledge accumulation on its biological roles in human pathology is being accelerated by its genetic, physiological, and pharmacological approaches. Owing to the ...

The transient receptor potential V1, or TRPV1, channel has a complex polymodal activation profile that integrates information from membrane potential changes, heat, and protons in addition to channel gating following ligand binding. TRPV1 is expressed along the peripheral pain pa ...

TRPP ion channels assemble with polycystin-1 family proteins into receptor-channel complexes. TRPP2–Polycystin-1 is required to coordinate renal three-dimensional tissue organization, whereas TRPP2–PKD1L1 is essential for establishment of left–right asymmetry du ...

So far the major focus of Transient Receptor Potential (TRP) channels in the context of pathophysiological disorders was centered exclusively on the ionic conductivity mediated by these channels. However, recently the importance of non-ionic functions of TRP channels in different p ...

This introduction lists TRP channels as possible pharmaceutical targets and will also refer to some methodological and still scientific caveats. First, it will be highlighted which scientific problems are still necessary to solve, including permeation, gating regulation. This p ...

Escalating problems with drug resistance continue to compromise the effectiveness of commercial antibiotics, necessitating the search for novel classes of antimicrobial agents. To circumvent problems with resistance, a multitarget single-pharmacophore approach has b ...

The capability to accurately, rapidly, and reproducibly determine the affinity of a ligand for a target protein or enzyme is a vital component for a successful structure-based drug design effort. In order to successfully drive a structure-based drug design (SBDD) project forward, multip ...

Crystallographic fragment screening is a technique for initiating drug discovery in which protein crystals are soaked or grown with high concentrations of small molecule compounds (typically MW 110–250 Da) chosen to represent fragments of potential drugs. Specific binding of the ...

The use of 3D structures derived from X-ray crystal data in drug development has increased in recent years. Molecular graphics applications are important tools at the end of the data processing pipeline and provide means to build, refine and validate protein models and ligand structures. We de ...

X-ray diffraction experiments on protein crystals are at the core of the structure determination process. An overview of X-ray sources and data collection methods to support structure-based drug design (SBDD) efforts is presented in this chapter. First, methods of generating and manip ...