Beta-receptor blockade by propranolol modifies the effect of the inhibitory, endogenous epidermal pentapeptide on epidermal cell flux at the G2-M transition but not at the G1-S transition.
The mitosis inhibitory pentapeptide, pGlu-Glu-Asp-Ser-GlyOH (EPP), which was isolated from mouse epidermis extracts, belongs to a group of growth inhibitory peptides that all have pyroglutamyl at the N-terminal end. Earlier experiments with crude or partially purified skin extracts have shown that the inhibitory effect could be enhanced by beta-receptor 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 significantly modifies the effect of EPP on mouse epidermal cell proliferation, as estimated by using a metaphase-arrest technique (Colcemid) to estimate the G2-M cell flux. The interaction between propranolol and EPP is complex; only the EPP-induced inhibition of the G2-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 followed by a dose-related and transient increase in the epidermal mitotic rate. The phosphodiesterase inhibitor caffeine had no effect on its own on epidermal cell proliferation but counter-acted the late (18-21 h) EPP-induced inhibition.
Elgjo
K
K
Institute of Pathology, National Hospital (Rikshospitalet), Oslo, Norway.
Reichelt
K L
KL
D000595:Amino Acid Sequence; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D005260:Female; D007399:Interphase / Q000187:drug effects; D051379:Mice; D008812:Mice, Hairless; D008938:Mitosis / Q000187:drug effects*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D011433:Propranolol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives
D009842:Oligopeptides; C050550:epidermal pentapeptide; D002110:Caffeine; D011433:Propranolol; D000242:Cyclic AMP; D011761:Pyrrolidonecarboxylic Acid