Current Pharmaceutical Biotechnology - Volume 12, Issue 1, 2011

It is my pleasure to introduce this “Hot Topic” special issue of Current Pharmaceutical Biotechnology, focusing on the family of cation channels that have attracted considerable attention and research work during the past decade as a target class for drug discovery. These channels are called the ‘transient receptor potential’ (TRP) ion channels because deletion of the trp gene, initially discovered in a fruit fly, caused the photorece Read More

Transient Receptor Potential channels are exquisite molecular transducers of multiple physical and chemical stimuli, hence the raising interest to study their relevance to Sensory Biology. Here we discuss a number of aspects of the biophysical and pharmacological properties of TRP channels, which we consider essential for a clear understanding of their sensory function in vivo. By examining concrete examples extracted from Read More

Cellular electrical activity is the result of a highly complex process that involve the activation of ion channel proteins. Ion channels make pores on cell membranes that rapidly transit between conductive and non-conductive states, allowing different ions to flow down their electrochemical gradients across cell membranes. In the case of neuronal cells, ion channel activity orchestrates action potentials traveling through axo Read More

Several of the 28 mammalian transient receptor potential (TRP) channel subunits are expressed throughout the alimentary canal where they play important roles in taste, chemo- and mechanosensation, thermoregulation, pain and hyperalgesia, mucosal function and homeostasis, control of motility by neurons, interstitial cells of Cajal and muscle cells, and vascular function. While the implications of some TRP channels, notabl Read More

Members of the classic type of transient receptor potential channels (TRPC) represent important molecules involved in hormonal signal transduction. TRPC3/6/7 channels are of particular interest as they are components of phospholipase C driven signalling pathways. Upon receptor-activation, G-protein-mediated stimulation of phospholipase C results in breakdown of phosphatidylinositides leading to increased intrac Read More

Unique among ion channels, TRPM6 and TRPM7 garnered much interest upon their discovery as the first ion channels to possess their own kinase domain. Soon after their identification, the two proteins were quickly linked to the regulation of magnesium homeostasis. However, study of their physiological functions in mouse and zebrafish have revealed expanding roles for these channel-kinases that include skeletogenesis and Read More

Transient receptor potential melastatin 8 (TRPM8) is a non-selective cation channel activated by cold temperature and cooling agents. TRPM8 is expressed in a subpopulation of cold-sensitive sensory neurons, as well as in the male urogenital system. TRPM8 is markedly upregulated in prostate cancer and in other tumors such as breast adenocarcinoma and melanoma. Moreover, recent studies suggest the potential inv Read More

Temperature perception is vital for cellular and metabolic homeostasis, avoidance, and survival. In the primary afferent nerve terminal, select members of the transient receptor potential (TRP) family of ion channels reside and convert thermal stimuli into neuronal activity. The cold and menthol receptor, TRPM8, is the predominant thermoceptor for cellular and behavioral responses to cold temperatures. Remarkably, thi Read More

Temperature sensing is a crucial feature of the nervous system, enabling organisms to avoid physical danger and choose optimal environments for survival. TRPM8 (Transient Receptor Potential Melastatin type 8) belongs to a select group of ion channels which are gated by changes in temperature, are expressed in sensory nerves and/or skin cells and may be involved in temperature sensing. This channel is activated b Read More

TRPV1 and TRPA1 have traditionally been considered to function independently from each other as homomers, but their extensive co-expression in sensory neurons and recent evidence suggest that these channels can functionally interact and may form a complex as part of their normal function. Although TRPA1 and TRPV1 do not absolutely require interaction to maintain function in expression systems or even sensory n Read More

Transient Receptor Potential Vanilloid Type 1 is a prominent “pain” receptor expressed in sensory afferent neurons. TRPV1 on peripheral nerve terminals detects a variety of noxious stimuli generated at sites of injury and inflammation, and in turn, drives the excitation and sensitization of C-fiber neurons. Significantly, TRPV1 is also located on the central terminals of sensory neurons projecting to the spinal cord and brainste Read More

The cloning of the first sensory Transient Receptor Potential (TRP) channel, TRPVanilloid 1 (TRPV1) in 1997, initiated a new era of pain research and coincided with the Decade of Pain Control and Research promulgated by the United States Congress. When cloned, TRPV1 channel was shown to be predominantly expressed in nociceptors (C- and A -fibers) and are activated by physical and chemical stimuli. Channel function can be a Read More

Elaboration of the structure of TRPV1 and its functional relationship with channel activity is a work in progress, with much remaining to be done before the structure-function relationship of TRPV1 is comprehensively elicited. The result is that the present state of knowledge can reasonably be described as a patch-work of insightful data where major deficits in knowledge remain and where meaningful general conclusions canno Read More

Capsaicin and other vanilloids selectively excite and subsequently desensitize pain-conducting nerve fibers (nociceptors) and this process contributes to the analgesic (and thus therapeutically relevant) effects of these compounds. Such a desensitization process is triggered by the activation of the transient receptor potential vanilloid subtype 1 receptor channels (TRPV1) that open their cationic pores, permeable to Read More

The transient receptor potential vanilloid type 1 ion channel (TRPV1) was identified as a receptor responsible for mediating the intense burning sensation following exposure to heat greater than ∼43 °C, or to capsaicin, the pungent ingredient of hot chilli peppers. More importantly, however, it has been shown that TRPV1 plays a pivotal role in the development of the burning pain sensation associated with inflammation in peri Read More