Effects of novel synthesized retinobenzoic acid (Am-80) on adenylate cyclase and arachidonic acid release in pig epidermis.
It has been well established that the psoriatic hyperproliferative epidermis is characterized by a defective beta-adrenergic adenylate cyclase response and an increased arachidonic acid metabolism. Effects of a newly synthesized retinoid, Am-80 (4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino) carbamoyl]benzoic acid), on the beta-adrenergic adenylate cyclase response and on the arachidonic acid metabolism of pig epidermis were investigated. Am-80 augmented the beta-adrenergic adenylate cyclase response of the epidermis. The effect was observed at the concentrations of more than 1 microM. The maximum beta-adrenergic augmentation effect induced by Am-80 was similar to those of all-trans-retinoic acid and of hydrocortisone. Am-80 inhibited the basal arachidonic acid release as well as 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated arachidonic acid release from epidermal keratinocytes. The effect was observed at the concentrations of 50-100 microM. The inhibitory effect of Am-80 was similar to those of all-trans-retinoic acid and of hydrocortisone. Our results indicate that Am-80, a newly synthesized retinoid, reveals the beta-adrenergic adenylate cyclase response augmentation effect and the inhibitory effect on the arachidonic acid metabolism of the epidermis. These effects are consistent with a view that Am-80 is another retinoid which has significant pharmacological effects on keratinocytes.
Koizumi
H
H
Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
Sato
K C
KC
Ohkawara
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D001565:Benzoates; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; D016718:Arachidonic Acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate