Characterization of alpha- and beta-adrenergic agonist stimulation of adenylate cyclase activity in human epidermal keratinocytes in vitro.

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 alpha- and beta-receptor subtypes, we have characterized the adrenergic receptor coupled to adenylate cyclase in cultured human epidermal keratinocytes. The relative potency order of stimulation of adenylate cyclase was: isoproterenol greater than epinephrine much greater than norepinephrine. The predominant adrenergic receptor is of the beta 2-subtype, as also confirmed by use of the selective antagonists propranolol, butoxamine, and atenolol. No evidence of alpha-adrenergic receptor mediation of adenylate cyclase was noted with the alpha 2-specific agonist, clonidine. Phenylephrine, the alpha 1-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 beta-adrenergic receptor potency order properties throughout growth and maturation.