Khellin, but not 8-methoxypsoralen, inhibits adenylyl cyclase system in HeLa cells.
Until recently, the therapeutic effects of furocoumarins and furochromones plus UV-A light were thought to be due to their ability to form photoadducts with DNA in the cell nuclei; now it appears that membrane effector systems may be involved as targets. Here we show that in HeLa cells khellin at 1 and 5 microM final concentration, in combination with UV-A light, inhibits NaF-stimulated adenylyl cyclase activity and Pertussis Toxin (PT)-catalyzed ADP-ribosylation of alpha-subunits of inhibitory guanine nucleotide regulatory proteins (Gi) and increases GTPase activity. In the same experimental conditions, 8-methoxypsoralen (8-MOP), either alone or plus UV-A, does not affect adenylyl cyclase and GTPase activities. Our results suggest that in HeLa cells, through an interaction with a receptor and the mediation of Gi proteins, the adenylyl cyclase system is a target for khellin but not for 8-MOP.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000528:radiation effects; D003624:Darkness; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007666:Khellin / Q000494:pharmacology*; D008566:Membranes / Q000378:metabolism; D008730:Methoxsalen / Q000494:pharmacology*; D037342:Pertussis Toxin; D014466:Ultraviolet Rays; D010566:Virulence Factors, Bordetella / Q000378:metabolism
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D007666:Khellin; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008730:Methoxsalen