Kondratskyi A. Expression and regulation of cold receptor TRPM8 in neuronal and epithelial tissues

The thesis is devoted to investigation of expression of cold receptor TRPM8 in the rat prostate and DRG neurons as well as to research of mechanisms of regulation of TRPM8 by steroid hormones and receptors, coupled to G-protein. Our data show that prostate secretory epithelial cells express functional TRPM8 on the plasmalemma. We also report, that 89% of TRPM8-expressing DRG neurons express hyperpolarization-activated channels, which makes its presence reliable, though not absolute, criterion for pre-selection of such neurons. Here we also show, that female mice displayed lower threshold for the sensation of cooling temperatures in the range of 15-25С compared to males and that these differences are due to regulation of TRPM8 by testosterone. Testosterone inhibits TRPM8 channel via a non-genomic pathway which involves a putative membrane receptor coupled to the Gi protein, adenylate cyclase (AC) and cAMP. Estradiol was not effective in the regulation of TRPM8 activity. Our data also demonstrate the regulation of TRPM8 by alpha2adrenoreceptors (alpha2AR). Activation of alpha2AR leads to the inhibition of TRPM8 via Gi protein/AC/cAMP/protein kinase A (PKA) signaling pathway. We conclude that TRPM8 downregulation via alpha2AR could have an impact in nociception, notably in cold allodynia during chronic constrictive nerve injury. Key words: TRP channels, cold receptor TRPM8, prostate, DRG neurons, testosterone, alpha2adrenoreceptor, G-protein.