"Ischemic" rise of epidermal cyclic AMP is a beta-adrenergic adenylate cyclase-dependent process.
The endogenous level of epidermal cyclic AMP does not remain constant but increases rapidly and transiently after removal of the tissue; this is known as the "ischemia" effect. UVB-irradiated epidermis which shows increased beta-adrenergic response revealed an increased ischemia effect, while psoriatic involved epidermis which shows decreased beta-adrenergic response revealed a decreased ischemia effect. Because of the similar rise-and-fall pattern between the ischemia effect and the beta-adrenergic response, the mechanism of the ischemia effect was investigated, especially in terms of the beta-adrenergic relationship. The ischemic rise of epidermal cyclic AMP was well preserved after 6 h pretreatment at 4 degrees C, and, following the pretreatment, the skin markedly increased its cyclic AMP level by the 37 degrees C treatment with 1 mM isobutylmethyl xanthine. The addition of propranolol or cimetidine at the time of 37 degrees C treatment (following the 4 degrees C pretreatment) had no effect on the ischemia effect; both skin groups markedly increased their cyclic AMP levels to an extent similar to that of the control skin. However, the addition of propranolol at the time of both preincubation (at 4 degrees C) and incubation (at 37 degrees C) markedly decreased the ischemic rise of cyclic AMP. Similar treatment by cimetidine had no effect on the ischemia effect. There was no significant difference in cyclic AMP phosphodiesterase activities among skin groups by propranolol or cimetidine pretreatment. These results indicate that the so-called ischemic rise of epidermal cyclic AMP is actually the beta-adrenergic adenylate cyclase-dependent process. Our results also indicate that the magnitude of the "ischemic" rise of cyclic AMP is generally parallel to the beta-adrenergic responsiveness of epidermis.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis*; D005260:Female; D006801:Humans; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012867:Skin / Q000032:analysis / Q000098:blood supply* / Q000528:radiation effects; D013696:Temperature
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine