Pharmacological inhibition of outwardly rectifying Cl- currents in rat peritoneal mast cells: a comparison of different stilbene derivatives.
Diethylstilbestrol and other stilbene derivatives can provide some inhibition of the outwardly rectifying Cl- current (I(Cl-,OR)) in rat peritoneal mast cells. In order to elucidate structure-activity relationships of diethylstilbestrol, 12 stilbenes as well as 17beta-estradiol and hexestrol were tested in rat peritoneal mast cells using the nystatin-perforated patch approach of the whole-cell patch-clamp technique. Since trans-stilbene showed no effect, the substituents of diethylstilbestrol must be of importance. The introduction of only one hydroxy group in trans-stilbene produced potent inhibition of the I(Cl-,OR) (IC50: 3.3 microM). But in contrast, resveratrol with hydroxy groups at positions 4, 3', and 5' as well as methoxy substituted stilbene derivatives and 17beta-estradiol were ineffective. On the other hand, hexestrol potently inhibited I(Cl-,OR) indicating that the aromatic ring systems can also be connected by an ethyl bridge. In summary, a hydroxy group at position 4 (or 4') is a prerequisite for diethylstilbestrol-mediated inhibition of I(Cl-,OR).
Institute of Pharmacology, University of Kiel, Hospitalstr 4, D-24105 Kiel, Germany.
Tim
T
Roloff
Albrecht
A
Ziegler
Dieter
D
Heber
Jörg
J
Seebeck
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002469:Cell Separation; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D005089:Exocytosis / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D008968:Molecular Conformation; D018408:Patch-Clamp Techniques; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
D018118:Chloride Channels; D017366:Serotonin Receptor Agonists; D013267:Stilbenes; D012701:Serotonin