title: Multiple-signaling pathways are involved in the inhibitory effects of galangin on urinary bladder contractility.
abstract: OBJECTIVE
  Flavonoids comprise a large group of natural polyphenolic compounds, which possess a wide spectrum of physiological and pharmacological effects. Recently, the flavonoid galangin was found to modulate smooth muscle contractility. The aim of the present study was to investigate the mechanism of actions of galangin on pig bladder smooth muscle and to characterize its potential as an alternative inhibitor of bladder smooth muscle contraction.
  
  
  METHODS
  Strips of pig detrusor muscle were mounted in separate 6-ml organ baths containing Krebs solution. The contractile response to carbachol (10(-8)-10(-4)M), potassium (2x10(-2)-10(-1)M), and electrical field stimulation-EFS (2-32 Hz) were determined before and after the addition of galangin (3x10(-5)M). The contractile responses to carbachol in calcium-free Krebs' solution plus EGTA and L-type channel blocker were determined in the absence and presence of the flavonoid. Furthermore, the effect of galangin was also evaluated after the administration in the bath of a number of antagonists/inhibitors including a combination of propranolol, phentolamine, capsazepine, and verapamil. Student's t-test and one factor ANOVA were used to determine the statistical significance of the effects.
  
  
  RESULTS
  Galangin inhibited the maximal contractile response to carbachol and potassium by 57.41% (P<0.01) and 33.52% (P<0.05), respectively. The maximum force of the carbachol-evoked contractions in calcium-free solution after incubation with galangin was 32% of the maximum initial force (Emax.initial: 5.8387+/-0.72 mN, Emax.Galangin: 1.9157+/-0.30 mN, P<0.01). The maximal contractile responses to EFS at 2, 4, 8, 16, and 32 Hz were reduced, compared to control, by 91.61% (P<0.01), 79.46% (P<0.01), 70.54% (P<0.01), 61.10% (P<0.01), and 9.8% (P>0.05), respectively. The inhibitory effect of galangin was unaffected by a combination of propranolol, phentolamine, and capsazepine (P>0.05). However, when verapamil was added to the medium, the inhibitory effects of galangin were partially blocked.
  
  
  CONCLUSIONS
  Galangin, at high concentrations, exerts an inhibitory effect on pig bladder smooth muscle contractility through the inhibition of calcium influx and the modulation of intracellular calcium movement. Furthermore, we have demonstrated that the inhibitory effect of galangin involves, at least in part, L-type calcium channels pathways.
authors.affiliation: Department of Urology, University of Maastricht, Maastricht, The Netherlands. miriamdambros@yahoo.com.br
authors.forename: Miriam
authors.initials: M
authors.lastname: Dambros
authors.forename: Rik
authors.initials: R
authors.lastname: de Jongh
authors.forename: Gommert A
authors.initials: GA
authors.lastname: van Koeveringe
authors.forename: Marjanka
authors.initials: M
authors.lastname: van Deutekom
authors.forename: Jo G R
authors.initials: JG
authors.lastname: De Mey
authors.forename: Paulo C R
authors.initials: PC
authors.lastname: Palma
authors.forename: Philip E V
authors.initials: PE
authors.lastname: van Kerrebroeck
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D003864:Depression, Chemical; D004558:Electric Stimulation; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D005419:Flavonoids; D018722:Nicotinic Agonists; C037032:galangin; D002217:Carbachol; D009543:Nifedipine; D011188:Potassium