Discrete expression of TRPV2 within the hypothalamo-neurohypophysial system: Implications for regulatory activity within the hypothalamic-pituitary-adrenal axis.
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.
Wainwright
Anna
A
Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, Essex CM20 2QR, United Kingdom.
Rutter
A Richard
AR
Seabrook
Guy R
GR
Reilly
Kathryn
K
Oliver
Kevin R
KR
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D015220:Calcium Channels / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015870:Gene Expression; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008252:Macaca fascicularis; D018613:Microscopy, Confocal / Q000379:methods; D010121:Oxytocin / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011863:Radioimmunoassay / Q000379:methods; D050916:TRPV Cation Channels; D014162:Transfection / Q000379:methods; D014667:Vasopressins / Q000378:metabolism
D015220:Calcium Channels; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; D014667:Vasopressins; D010121:Oxytocin; D003346:Corticotropin-Releasing Hormone