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.
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Iizuka
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Watanabe
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Ohkawara
D017255:Acitretin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004817:Epidermis / Q000201:enzymology*; D004837:Epinephrine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013552:Swine; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D014212:Tretinoin; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid; D006632:Histamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D017255:Acitretin; D004837:Epinephrine