BETA-RECEPTOR BLOCKADE BY PROPRANOLOL MODIFIES THE EFFECT OF THE INHIBITORY, ENDOGENOUS EPIDERMAL PENTAPEPTIDE ON EPIDERMAL-CELL FLUX AT THE G(2)-M TRANSITION BUT NOT AT THE G(1)-S TRANSITION

The mitosis inhibitory pentapeptide, pGlu-Glu-Asp-Ser-GlyOH (EPP), whi ch was isolated from mouse epidermis extracts, belongs to a group of g rowth inhibitory peptides that all have pyroglutamyl at the N-terminal end. Earlier experiments with crude or partially purified skin extrac ts have shown that the inhibitory effect could be enhanced by beta-rec eptor agonists and by dibutyryl cAMP, and that beta-receptor blockade could neutralise it. We now show that treatment with the beta receptor blocker propranolol before or after EPP treatment of hairless mice si gnificantly modifies the effect of EPP on mouse epidermal cell prolife ration, as estimated by using a metaphase-arrest technique (Colcemid) to estimate the G(2)-M cell flux. The interaction between propranolol and EPP is complex; only the EPP-induced inhibition of the G(2)-M cell flux was modified by beta-receptor blockade, while the late (18-21 h) inhibition of the mitotic rate was unaltered. Propranolol alone was f ollowed by a dose-related and transient increase in the epidermal mito tic rate. The phosphodiesterase inhibitor caffeine had no effect on it s own on epidermal cell proliferation but counter-acted the late (18-2 1 h) EPP-induced inhibition.