On the lack of response to catecholamine stimulation by the adenyl cyclase system in psoriatic lesions.
When epidermis from the uninvolved skin of psoriatic patients was incubated for 5 min in Hank's medium containing adrenaline and theophylline, the cyclic AMP level consistently increased 20-30 times over the level observed when adrenaline was not added to the medium. On the other hand, when epidermis from the involved skin of psoriatic patients was incubated under the same experimental conditions, the cyclic AMP level increased only 2-5 times. Even when theophylline, and inhibitor of specific cyclic AMP-phosphodiesterase, was omitted from the medium, a clearly demonstrable difference in sensitivity to adrenaline was evident in normal appearing and lesional psoriatic epidermis. These results indicate a faulty adenyl cyclase system in the involved epidermis of psoriatic lesions rather than a defective degradation process by the specific phosphodiesterase. Since the Km for adrenaline activation of adenyl cyclase was approximately the same in both the uninvolved and the involved epidermis and since the cyclic AMP increase by adrenaline was abolished by the addition of propranolol, the basic nature of the beta-receptor (specifically the binding affinity to adrenaline) in the involved epidermis does not appear to be defective. On the other hand, the finding that the Vmax for adrenaline activation is 10-20 times higher in the uninvolved than in the involved epidermis suggests that the poor response in the involved epidermis may be due to fewer available binding sites for adrenaline in the psoriatic lesion.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D011565:Psoriasis / Q000201:enzymology*; D012867:Skin / Q000201:enzymology; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors
D011433:Propranolol; D013806:Theophylline; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D004837:Epinephrine