Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures.
The vanilloid receptor subtype 1 (VR1)/(TRPV1), binding capsaicin, is a non-selective cation channel that recently has been shown in human keratinocytes in vitro and in vivo. However, a description of VR1 localization in other cutaneous compartments in particular cutaneous nerve fibers is still lacking. We therefore investigated VR1 immunoreactivity as well as mRNA and protein expression in a series (n = 26) of normal (n = 7), diseased (n = 13) [prurigo nodularis (PN) (n = 10), generalized pruritus (n = 1), and mastocytosis (n = 2)], and capsaicin-treated human skin (n = 6). VR1 immunoreactivity could be observed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands. Upon reverse transcriptase-polymerase chain reaction and Western blot analysis, VR1 was detected in mast cells and keratinocytes from human skin. In pruritic skin of PN, VR1 expression was highly increased in epidermal keratinocytes and nerve fibers, which was normalized after capsaicin application. During capsaicin therapy, a reduction of neuropeptides (substance P, calcitonin gene-related peptide) was observed. After cessation of capsaicin therapy, neuropeptides re-accumulated in skin nerves. In conclusion, VR1 is widely distributed in the skin, suggesting a major role for this receptor, e.g. in nociception and neurogenic inflammation.
Department of Dermatology, University of Münster, Muenster, Germany. sonja.stander@uni-muenster.de
Sonja
S
Ständer
Corinna
C
Moormann
Mark
M
Schumacher
Jörg
J
Buddenkotte
Metin
M
Artuc
Victoria
V
Shpacovitch
Thomas
T
Brzoska
Undine
U
Lippert
Beate M
BM
Henz
Thomas A
TA
Luger
Dieter
D
Metze
Martin
M
Steinhoff
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D001921:Brain / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D002211:Capsaicin / Q000378:metabolism / Q000627:therapeutic use; D002460:Cell Line; D002648:Child; D004439:Eccrine Glands / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000294:innervation* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism; D009475:Neurons, Afferent / Q000502:physiology* / Q000648:ultrastructure; D009619:Nociceptors / Q000502:physiology; D011537:Pruritus / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism; D012627:Sebaceous Glands / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013373:Substance P / Q000378:metabolism
D011955:Receptors, Drug; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin