The opioid growth factor, [Met(5)]-enkephalin, inhibits DNA synthesis during recornification of mouse tail skin

Opioid peptides serve as tonically active negative growth regulators in ren ewing 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, naltr exone (NTX, 20 mg/kg i.p.) following injury. Blockade of opioidreceptor int eraction by NTX for 4 h resulted in an elevation of 36-66% in basal cell DN A synthesis measured 24 h after injury. Injection of the endogenous opioid peptide, [Met(5)]-enkephalin (OGF, 10 mg/kg i.p.) 4 h before termination, s uppressed radiolabelled thymidine incorporation in the basal cell layer by 37-46% at 24 h after wounding. The magnitude of the effects on DNA synthesi s of OGF, but not NTX, depended on the timing of administration with respec t 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 d osage 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 sk in. These results indicate: (a) a native opioid peptide and its receptor ar e expressed in epidermal cells of injured and uninjured mouse tail skin; (b ) removal of the stratum corneum by tape stripping does not disrupt the fun ction of the endogenous opioid growth system; (c) the proliferative respons e to wounding of the tail is tonically inhibited by the receptor-mediated a ction of an endogenous opioid peptide; and (d) DNA synthesis by basal cells can be elevated by disrupting opioid peptidereceptor interactions.