Characterization of α- and β-Adrenergic Agonist Stimulation of Adenylate Cyclase Activity in Human Epidermal Keratinocytes In Vitro

Abstract

Adrenergic receptors are responsible for selective recognition and binding of catecholamines and may in turn have an effect on epidermal cell growth and maturation via adenosine-3',5'-monophosphate (cAMP). Using endogenous catecholamines and drugs specific for α- and β-receptor subtypes, we have characterized the adrenergic receptor coupled to adenylate cyclase in cultured human epidermal keratinocytes. The relative potency order of stumulation of adenylate cyclase was: isoproterenol > epinephrine >> norepinephrine. The predominant adrenergic receptor is of the β2-subtype, as also confirmed by use of the selective antagonists propranolol, butoxamiine, and atenolol. No evidence of α-adrenergic receptor mediation of adenylate cyclase was noted with the α2-specific agonist, clonidine. Phenylephrine, the α1-specific agonist, affected cAMP formation but this response could not be totally inhibited with prazosin, suggesting an unknown mechanism of action. Human keratinocytes retained the same β-adrenergic receptor potency order properties throughout growth and maturation