Epinephrine synthesis in rat skin by an N-methyltransferase

Homogenates of rat skin N-methylated norepinephrine to form epinephrine. In the brain and adrenal medulla the enzyme phenylethanolamine-N-methyltransferase synthesizes epinephrine, but the skin epinephrine forming enzyme was an N-methyltransferase distinct from phenylethanolamine-N-methyltransferase. Skin N-methyltransferase was not inhibited by the phenylethanolamine-N-methyltransferase inhibitor SKF 29661. Unlike phenylethanolamine-N-methyltransferase, skin readily methylated dopamine to form epinine. Sympathetic denervation by superior cervical ganglionectomy had no effect on skin N-methyltransferase levels. Procedures that reduced skin norepinephrine levels to 2% of control left skin epinephrine levels at 38% of control even when plasma epinephrine levels were very low. Skin contains an extraneuronal enzyme that synthesizes epinephrine in vitro and appears to synthesize part of the epinephrine normally present in skin. The enzyme can synthesize epinephrine and epinine, both of which can regulate epidermal proliferation, skin blood flow, and atopic responses.