P2X purinergic receptor antagonist accelerates skin barrier repair and prevents epidermal hyperplasia induced by skin barrier disruption.
The effects of ATP receptor agonists/antagonists on skin barrier recovery rate were evaluated in hairless mice. Topical application of ATP and alpha,beta-methylene ATP (agonist of P2X receptor) delayed barrier recovery. Topical application of suramin (nonspecific ATP receptor antagonist), pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (P2X receptor antagonist), and 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP) (P2X1, P2X3, P2X2/3 antagonist) after barrier disruption accelerated the barrier repair. The P2Y type receptor antagonist Reactive Blue 2 did not affect the barrier repair process. Moreover, topical application of TNP-ATP prevented epidermal hyperplasia induced by barrier insult under low environmental humidity. ATP was secreted immediately after tape stripping on skin in organ culture. alpha,beta-Methylene ATP increased intercellular calcium in cultured keratinocytes and the increase was blocked by TNP-ATP. Both reverse transcription polymerase chain reaction assay and immunohistochemical study showed the existence of protein that had a structure similar to P2X3 on hairless mouse epidermis. These results suggest that cutaneous barrier homeostasis can be regulated by cation flux through a P2X3-like ATP receptor.
Denda
Mitsuhiro
M
Shiseido Research Center, 2-12-1 Fukuura, Kanazawa-ku, Yokohama, Japan. hiro.denda@to.shiseido.co.jp
Inoue
Kaori
K
Fuziwara
Shigeyoshi
S
Denda
Sumiko
S
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D005456:Fluorescent Dyes / Q000494:pharmacology; D006965:Hyperplasia; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013498:Suramin / Q000494:pharmacology*; D014867:Water / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D010975:Platelet Aggregation Inhibitors; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D014867:Water; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium