Mechanisms involved in kaempferol-induced relaxation in rat uterine smooth muscle.
The effect of kaempferol on KCI (60 mM)-induced tonic contraction in isolated rat uterus and its modification by inhibitors of cAMP-dependent protein kinase (PKA) (Rp-cAMPS and TPCK), phosphodiesterase (papaverine), adenylyl cyclase (2',3'-dideoxyadenosine, DDA), transcription (actinomycin D), protein synthesis (cycloheximide) and ornithine decarboxylase (alpha-difluoromethyl-ornithine, DFMO), as well as a polyamine, spermine, have been assayed. Kaempferol (3 to 60 microM) induced concentration-dependent relaxation on KCl-induced tonic contraction (IC50: 10.1 +/- 1.89 microM). This relaxing effect was antagonized (p<0.05) by Rp-cAMPS (10 microM), TPCK (3 microM), DDA (100 microM), actinomycin D (4 and 12 microM), cycloheximide (100 microM), DFMO (10 mM), actinomycin D (12 microM) plus TPCK and actinomycin D (12 microM) plus spermine (1 mM). Furthermore, the displacement obtained with actinomycin D plus DFMO was not statistically significant. Our results suggest that kaempferol through cAMP produces transcriptional events and polyamines are, at least partially, involved in the relaxant effect of kaempferol.
Revuelta
M P
MP
Farmacología, Dpto Medicina, Facultad de Medicina, Universidad de Oviedo, Spain.
Cantabrana
B
B
Hidalgo
A
A
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000494:pharmacology; D004357:Drug Synergism; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids; D066298:In Vitro Techniques; D044949:Kaempferols; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology
D000067956:Adenylyl Cyclase Inhibitors; D000963:Antimetabolites; D004791:Enzyme Inhibitors; D005419:Flavonoids; D044949:Kaempferols; D010726:Phosphodiesterase Inhibitors; D011500:Protein Synthesis Inhibitors; D015842:Serine Proteinase Inhibitors; D013873:Thionucleotides; D003609:Dactinomycin; C016957:adenosine-3',5'-cyclic phosphorothioate; D013096:Spermine; D014108:Tosylphenylalanyl Chloromethyl Ketone; D016048:Dideoxyadenosine; D011189:Potassium Chloride; C006552:kaempferol; D003513:Cycloheximide; D011794:Quercetin; D010208:Papaverine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000518:Eflornithine