title: The opioid growth factor, [Met5]-enkephalin, inhibits DNA synthesis during recornification of mouse tail skin.
abstract: Opioid peptides serve as tonically active negative growth regulators in renewing and regenerating epithelia. To examine the involvement of opioids in renewal of the stratum corneum after tape stripping of tail skin, C57BL/6 J mice were given systemic injections of the potent opioid antagonist, naltrexone (NTX, 20 mg/kg i.p.) following injury. Blockade of opioid-receptor interaction by NTX for 4 h resulted in an elevation of 36-66% in basal cell DNA synthesis measured 24 h after injury. Injection of the endogenous opioid peptide, [Met5]-enkephalin (OGF, 10 mg/kg i.p.) 4 h before termination, suppressed radiolabelled thymidine incorporation in the basal cell layer by 37-46% at 24 h after wounding. The magnitude of the effects on DNA synthesis of OGF, but not NTX, depended on the timing of administration with respect to injury. OGF maximally depressed basal cell labelling (72%) when given 16 h after tape stripping. Concomitant administration of naloxone (10 mg/kg) with OGF blocked the inhibition of DNA synthesis; naloxone alone at the dosage utilized had no effect on cell labelling. Both OGF and its receptor, OGFr, were detected by immunocytochemistry in the basal and suprabasal cell layers, but not the cornified layer of tape stripped and uninjured tail skin. These results indicate: (a) a native opioid peptide and its receptor are expressed in epidermal cells of injured and uninjured mouse tail skin; (b) removal of the stratum corneum by tape stripping does not disrupt the function of the endogenous opioid growth system; (c) the proliferative response to wounding of the tail is tonically inhibited by the receptor-mediated action of an endogenous opioid peptide; and (d) DNA synthesis by basal cells can be elevated by disrupting opioid peptide receptor interactions.
authors.affiliation: Department of Comparative Medicine, College of Medicine, The Pennsylvania State University, Hershey 17033-2390, USA. rpw4@psu.edu
authors.forename: R P
authors.initials: RP
authors.lastname: Wilson
authors.forename: P J
authors.initials: PJ
authors.lastname: McLaughlin
authors.forename: C M
authors.initials: CM
authors.lastname: Lang
authors.forename: I S
authors.initials: IS
authors.lastname: Zagon
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000293:injuries; D006133:Growth Substances / Q000494:pharmacology*; D015603:Keratinocytes / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011957:Receptors, Opioid / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D013623:Tail; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium; D014945:Wound Healing / Q000187:drug effects
chemical_list: D006133:Growth Substances; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C033593:methionine-enkephalin receptor; D014316:Tritium; D004744:Enkephalin, Methionine; D009271:Naltrexone; D004247:DNA; D013936:Thymidine