Glucocorticoid-induced modulation of the beta-adrenergic adenylate cyclase response of epidermis: its relation to epidermal phospholipase A2 activity.
It has been suggested that glucocorticoids produce their biologic effects through the synthesis of phospholipase A2 inhibitor protein (lipocortin) in various cell systems. Recent studies from our laboratory revealed that glucocorticoids augment the beta-adrenergic adenylate cyclase response of epidermis and that this effect depends on a protein synthesis mechanism. In order to elucidate the possible mechanism of this glucocorticoid effect in terms of phospholipase A2 activity, an in vitro pig skin incubation system was employed. Mepacrine, a phospholipase A2 inhibitor, augmented the beta-adrenergic adenylate cyclase response of epidermis as glucocorticoids. The effect of mepacrine was stronger and was observed earlier than that of glucocorticoid (hydrocortisone). The addition of both mepacrine and hydrocortisone at their optimal concentrations in the incubation medium, resulted in neither an additive nor a synergistic effect on the beta-adrenergic augmentation. On the other hand, melittin, a phospholipase A2 stimulator, depressed the beta-adrenergic adenylate cyclase response. The addition of both melittin and hydrocortisone in the incubation medium resulted in the inhibition of the hydrocortisone-induced beta-adrenergic augmentation effect. Following long-term incubation with hydrocortisone, the epidermal phospholipase A2 activity was significantly decreased. These results indicate that glucocorticoids might affect the beta-adrenergic adenylate cyclase response of epidermis through the synthesis of phospholipase A2 inhibitor protein (lipocortin) as in other cell systems.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D017302:Annexins; D004817:Epidermis / Q000201:enzymology*; D006023:Glycoproteins / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008555:Melitten / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013552:Swine; D013997:Time Factors
D017302:Annexins; D006023:Glycoproteins; D011943:Receptors, Adrenergic, beta; D008555:Melitten; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000262:Adenylyl Cyclases; D011796:Quinacrine; D006854:Hydrocortisone