Background: Transient receptor potential (TRP) channels are a superfamily of ion
channels termed after the trp gene in Drosophila that are diverse in structure and control a wide
range of biological functions including cell development and growth, thermal regulation, and
vascular physiology. Of significant interest is the transient receptor potential cation channel
subfamily V member 1 (TRPV1) receptor, also known as the capsaicin receptor and the vanilloid
receptor 1, that is a non-selective cation channel sensitive to a host of external stimuli including
capsaicin and camphor, venoms, acid/basic pH changes, and temperature.
Methods: Given the multiple modalities that TRPV1 receptors impact in the body, we examined and
discussed the role of these receptors in vasomotor control, metabolic disorders, cellular injury,
oxidative stress, apoptosis, autophagy, and neurodegenerative disorders and their overlap with other
signal transduction pathways that impact trophic factors.
Results: Surprisingly, TRPV1 receptors do not rely entirely upon calcium signaling to affect cellular
biology, but also have a close relationship with the mechanistic target of rapamycin (mTOR), AMP
activated protein kinase (AMPK), and protein kinase B (Akt) that have roles in pain sensitivity, stem
cell development, cellular survival, and cellular metabolism. These pathways with TRPV1 converge
in the signaling of growth factors with recent work highlighting a relationship with erythropoietin
(EPO). Angiogenesis and endothelial tube formation controlled by EPO requires, in part, the
activation of TRPV1 receptors in conjunction with Akt and AMPK pathways.
Conclusion: TRPV1 receptors could prove to become vital to target disorders of vascular origin and
neurodegeneration. Broader and currently unrealized implementations for both EPO and TRPV1
receptors can be envisioned for for the development of novel therapeutic strategies in multiple
systems of the body.
Keywords: Akt, aging, aging-related disorders, Alzheimer’s disease, AMP activated protein kinase (AMPK), angiogenesis,
apoptosis, autophagy, cardiovascular disease, diabetes mellitus, endothelial cells, epidermal growth factor, erythropoietin,
hamartin (tuberous sclerosis 1)/tuberin (tuberous sclerosis 2) (TSC1/TSC2), endothelial cells, hyperthermia, mechanistic target
of rapamycin (mTOR), mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), metabolism, nerve growth factor,
nicotinamide, nicotinamide adenine dinucleotide (NAD+), proline rich Akt substrate 40 kDa (PRAS40), oxidative stress, pain,
phosphoinositide 3 –kinase (PI 3-K), programmed cell death, silent mating type information regulation 2 homolog 1
(Saccharomyces cerevisiae) (SIRT1), sirtuin, stem cells, thermoregulation, transient receptor potential, TRPV1, vanilloid
Rights & PermissionsPrintExport