Discrete expression of TRPV2 within the hypothalamo‐neurohypophysial system: Implications for regulatory activity within the hypothalamic‐pituitary‐adrenal axis

Abstract

Transient receptor potential channel proteins (TRPs) constitute a steadily growing family of ion channels with a range of purported functions. It has been demonstrated that TRPV2 is activated by moderate thermal stimuli and, in the rat, is expressed in medium to large diameter dorsal root ganglion neurons. In this study, antisera specific for the human TRPV2 homologue were raised and characterized for immunohistochemical use. Subsequently, thorough investigation was made of the localization of this cation channel in the macaque primate brain. TRPV2-immunoreactive material was highly restrictively localized to hypothalamic paraventricular, suprachiasmatic, and supraoptic nuclei. Confocal double- and triple-labeling studies demonstrated that TRPV2 immunoreactivity is preferentially localized to oxytocinergic and vasopressinergic neurons. Few, if any, cells in these regions expressed TRPV2 immunoreactivity in the absence of oxytocin immunoreactivity or vasopressin immunoreactivity. Expression in the paraventricular and supraoptic nuclei suggests that TRPV2 is likely to play a fundamental role in mediating cation transport in neurohypophysial neurons. TRPV2 has been shown to be translocated upon cell activation and neurons expressing TRPV2 immunoreactivity in vivo are among those known to engage in sporadic, intense activity. Taken together, these data suggest that this channel may play a vital role in mediating physiological activities associated with oxytocin and vasopressin release such as parturition, lactation, and diuresis. These data may also implicate the involvement of TRPV2 in disorders of the hypothalamic-pituitary-adrenal axis, including anxiety, depression, hypertension, and preterm labor.

Integration of thermal and osmotic regulation of water homeostasis: the role of TRPV channels

“…As shown in Fig. 3, it is prominently and preferentially expressed in the SON, PVN, and neural lobe in primates with coexpression in VP and OT neurons (86). It is also prominently expressed in rat SON, PVN, and neural lobe (31).…”

Oxytocin Stimulates Extracellular Ca2+ Influx Through TRPV2 Channels in Hypothalamic Neurons to Exert Its Anxiolytic Effects

“…OXT neurons express additional plasma membrane Ca 2+ channels, including the transient receptor potential (TRP), vanilloid type 2 (TRPV2) channel (Wainwright et al, 2004). It forms a Ca 2+ -conducting cation channel and was first found in sensory ganglia to be activated by heat (Caterina et al, 1999) and in aortic myocytes by cell swelling, the latter suggesting a role in osmoregulation (Muraki et al, 2003).…”

“…TRPV2 channels are expressed both peripherally and centrally; their physiological functions in the brain, however, are not well understood (Ramsey et al, 2006). Their expression in OXT-producing neurons, demonstrated in macaques (Wainwright et al, 2004), makes it possible that they are involved in the modulation of [Ca 2+ ] i in these cells, thus favoring a role of extracellular Ca 2+ in OXT-induced intracellular signaling and behavior. Indeed, we found that influx of extracellular Ca 2+ is necessary for MEK1/2 phosphorylation and the anxiolytic effect of OXT within the PVN.…”

Pharmacological Characterization and Molecular Determinants of the Activation of Transient Receptor Potential V2 Channel Orthologs by 2-Aminoethoxydiphenyl Borate

“…that TRIM inhibits oxytocin-induced neuronal firing in the supraoptic nucleus of the hypothalamus (Tobin et al, 2006), in which TRPV2 is highly expressed and localized on oxytocin neurons (Wainwright et al, 2004).…”