Cis-urocanic acid down-regulates histamine-mediated activation of adenylate cyclase in the pig epidermis.
Urocanic acid (UCA), one of the skin's major components for absorbing UV radiation, is present naturally in the stratum corneum as a trans-isomer. On absorption of UVB radiation either in vitro or in the skin, UCA undergoes trans- to cis-isomerization in a dose-dependent manner. Although the mechanism by which cis-UCA suppresses immunity remains unelucidated, recent studies have indicated that cis-UCA appears to inhibit the induction of cyclic AMP in fibroblasts, which suggests that this molecule plays an active role in modifications to the skin. Here, we report that although neither trans-UCA nor cis-UCA increases cyclic AMP in the pig epidermis, cis-UCA actively down-regulates the increase of cyclic AMP induced by histamine. The effects of cis-UCA on the pig epidermis are revealed through the modulation of the effects caused by histamine. These findings suggest that in the pig epidermis, the initial biochemical and cellular event for UVB-induced immune suppression--that is, the step immediately following the isomerization of trans-UCA to cis-UCA--is down-regulation of cyclic AMP brought about by the activity of cis-UCA.
Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
T
T
Shimizu
H
H
Koizumi
H
H
Nishino
R
R
Abe
A
A
Ohkawara
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects* / Q000201:enzymology; D006632:Histamine / Q000494:pharmacology*; D013237:Stereoisomerism; D013552:Swine; D014560:Urocanic Acid / Q000737:chemistry / Q000494:pharmacology*
D006632:Histamine; D000262:Adenylyl Cyclases; D014560:Urocanic Acid