Adrenergic mechanisms and the adenyl cyclase system in atopic dermatitis.
Patients with atopic dermatitis have abnormal autonomic responses of the arterioles, pilomotor smooth muscle, and sweat glands. Their lesions have been reported to contain increased amounts of the neurohumors, acetylcholine and norepinephrine, as well as increased activity of acetylcholinesterase and catechol-O-methyltransferase. In vitro studies of epidermis show that beta adrenergic agonists fail to evoke the normal inhibition of mitosis of basal cells of patients with atopic dermatitis. Epidermis removed not only from the lesions, but also from normal-appearing skin, responded abnormally. The increase in intracellular levels of cAMP after exposure to catecholamines was similar in normal and atopic epidermis. Lymphocytes and PMN leukocytes isolated from patients with atopic dermatitis show both a decreased physiologic response (glycogenolysis and inhibition of lysosome enzyme release) and a decreased rise in intracellular levels of cAMP upon incubation with beta agonists, but a normal response to PGE1. Cortisol increases the response of lymphocyte adenyl cyclase to both agonists and, in the case of the patients with atopic disease, more than overcomes the depressed response to beta agonists. Because the  leukocytes respond normally to PGE1 and because others have reported normal activities of skin and adenyl cyclase, phosphodiesterase, and protein kinases, we conclude that the step responsible for the diminished beta adrenergic response lies antecedent to the catalytic site of adenyl cyclase.
D000109:Acetylcholine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists; D001341:Autonomic Nervous System / Q000503:physiopathology*; D002395:Catecholamines / Q000494:pharmacology; D000242:Cyclic AMP; D003876:Dermatitis, Atopic / Q000503:physiopathology*; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D006003:Glycogen; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000109:Acetylcholine; D009638:Norepinephrine