Epinephrine induces β-adrenergic desensitization and differentiation of HL-60 cells

Abstract

The HL-60 cell line was cultured in a serum-free medium and exposed to various concentrations of EPI. The effects on cell growth, differentiation and β-adrenergic response were followed during the culture period of 72 h. Short term exposure (3min) to EPI (InM-ImM) in the presence of theophylline (4 HIM) caused a dose-dependent increase of cAMP levels with a maximum of 1500% above basal levels. When the cells were exposed to EPI (1 nM-10/μM) for 72 h, a dose-dependent increase of cAMP levels with a maximum of 60% above basal levels. Sustained exposure to EPI generated a dose-dependent desensitization of the β-adrenergic signal system. After EPI treatment for 72 h, IPR (10μM for 3min) in the presence of theophylline (4 HIM) increased cAMP-levels by only 80% above baseline level (cAMP levels after maintained exosure to EPI), compared to 1080% above unstimulated level in control cells. The a-adrenergic receptor blocker PHENT (10/μM) did not affect baseline cAMP level or IPR-dependent cAMP response, but a mixture of EPI and PHENT increased the response to IPR. The HL-60 cell growth was not influenced by EPI. However, after repeated exposure to EPI for 72 h a concentration-dependent increase of HL-60 differentiation was demonstrated. Differentiation was not influenced by PHENT. These results suggest a differentiation induction due to a β-adrenergic-induced cAMP elevation.

Key Words:

• β-adrenergic receptors
• cyclic AMP
• epinephrine
• desensitization
• differentiation
• HL-60 cells