Pulmonary, gastrointestinal and urogenital pharmacologyRelaxant mechanisms of 3, 5, 7, 3′, 4′-pentamethoxyflavone on isolated human cavernosum

We have investigated effects and mechanisms responsible for the activity of 3, 5, 7, 3′, 4′-pentamethoxyflavone (PMF) on isolated human cavernosum. PMF is the major flavone isolated from Kaempferia parviflora claimed to act as an aphrodisiac. PMF caused relaxation of phenylephrine precontracted human cavernosal strips, and this effect was slightly inhibited by NG-nitro-l-arginine, a nitric oxide synthase inhibitor, but not by ODQ (soluble guanylate cyclase inhibitor), TEA (tetraethylammonium, blocker of voltage-dependent K+ channels) or glybenclamide (blocker of ATP-dependent K+ channels). PMF did not significantly inhibit the relaxant activity of glyceryltrinitrate or acetylcholine on human cavernosal strips precontracted with phenylephrine. In contrast, sildenafil (phosphodiesterase inhibitor) potentiated the relaxant activity of glyceryl trinitrate but not of acetylcholine. In normal Krebs solution with nifedipine (blocker of l-type Ca2+ channels), or in Ca2+-free Krebs solution, PMF caused a further inhibition of human cavernosum contracted with phenylephrine. In human cavernosum treated with thapsigargin (inhibitor of sarcoplasmic reticulum Ca2+-ATPase) in Ca2+-free medium, PMF suppressed the concentration-response curve of human cavernosum to phenylephrine and a further suppression was found when SKF-96365 (a blocker of store-operated Ca2+ channels and Y-27632 (inhibitor of Rho-kinase)), but not nifedipine, were added sequentially. Thus, PMF had only a weak effect on the release of nitric oxide, and had no effect as a KATP- or KCa channel opener, a phosphodiesterase inhibitor, a store-operated Ca2+ channel blocker or a Rho-kinase inhibitor. Therefore, these studies suggest that PMF causes relaxation of human cavernosum through voltage-dependent Ca2+ channels and other mechanisms associated with calcium mobilization.

PMF inhibited L-type Ca2+ channel and mobilization of Ca2+ from sarcoplasmic reticulum (SR), and might (?) stimulate release of Ca2+ from other intracellular stores. PMF did not appear to affect (X) Ca-activated K-channels (Kca), ATP activated K-channels (KATP), store-operated channels (STOC), or Rhokinase.288