A new synthetic retinoid, E-5166, augments epidermal beta-adrenergic adenylate cyclase response

Effects of a new synthetic retinoid, 3, 7, 11, 15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166), on the cyclic AMP system of pig skin epidermis was investigated. When pig skin slices were incubated in vitro for 24 h, the beta-adrenergic adenylate cyclase response (epinephrine-induced cyclic AMP accumulation) was decreased. The addition of E-5166 in the incubation medium resulted in an increase of this receptor response of epidermis. On the other hand, histamine-induced cyclic AMP accumulations were decreased by the E-5166 treatment. The effect of E-5166 was concentration-dependent; the maximal effect was observed at 50-100 microM. Ro 10-1670 (an active derivative of Ro 10-9359 (etretinate)) is known to have similar beta-adrenergic augmentation effect. The simultaneous addition of E-5166 and Ro 10-1670 at their optimal concentrations resulted in neither additive nor synergistic effect on the epinephrine-induced cyclic AMP accumulations. There was no significant difference in cyclic AMP phosphodiesterase activity between control and E-5166-treated epidermis. These data indicate that pig skin epidermal adenylate cyclase responses are modulated by E-5166 probably through the same mechanism induced by other retinoids.