The transient receptor potential (TRP) family of proteins detects transient changes in the environment such as temperature and acidity and responds by altering their permeability to specific ions thereby modifying the membrane potential. Transient receptor potential vanilloid 1 (TRPV1) was the first of the temperature-activated TRP family to be cloned (Caterina ei a/., 1997) and is known to respond to capsaicin (Szallasi and Blumberg, 1999), various plant toxins (Szallasi and Blumberg, 1999), high temperatures (Caterina ei a/., 1997), low pH (Tominaga ei a/., 1998), and several inflammatory factors (De Petrocellis and Di Marzo, 2005; Tominaga and Caterina, 2004).
Capsaicin, the first identified TRPV1 ligand has a comparable structure to anandamide which led to investigation and subsequent reporting of anandamide as an additional ligand (Smart ei a/., 2000; Zygmunt ei a/., 1999). There has been some contention as to the labeling of anandamide as a TRPV1 agonist due to inconsistencies in the responses elicited by the ligand (reviewed in Starowicz ei a/., 2007). It seems likely however that this is an artifact of different experimental protocols and in particular sensitivity states of TRPV1. The phosphorylation state of the receptor alters the sensitivity threshold and hence the effective concentrations of anandamide or other stimulants required to elicit a response (De Petrocellis ei a/., 2001; Lee ei a/., 2005).
Many reports have described TRPV1 expression in varied tissues and cell types including neuronal cells of the central and peripheral nervous system (Birder ei a/., 2001; Caterina ei a/., 1997; Cristino ei a/., 2006; Mezey ei a/., 2000; Roberts ei a/., 2002; Toth ei a/., 2005), various subtypes of white blood cells (Chen ei a/., 2003; Heiner ei a/., 2003; Saunders ei a/., 2007), vascular endothelial cells (Golech ei a/., 2004), keratinocytes of the epidermis (Southall ei a/., 2003), beta-pancreatic cells (Akiba ei a/., 2004), and in cultured human lung and liver cells (Reilly ei a/., 2003). Anandamide is also synthesized by many peripheral and central cell types suggesting anandamide action on TRPV1 channels may have many widespread effects.
Unfortunately the specific pathways activated by TRPV1-mediated influx of Ca2+ are not yet known and are likely to vary depending on the individual intracellular proteome of the cells expressing TRPV1. So far most research into the functionality of the receptor has focused on a physiological response or detection of inward currents and increases in intracellular calcium, but no reports of the pathways linking these events. This work has, however, been crucial in assigning TRPV1 importance in several physiological processes. Certainly, signal transduction pathways generated by TRPV1 activation by heat are proving difficult to decipher and likely to vary considerably with regional and cellular differences (Rau et al, 2007).
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