title: 17β-Estradiol relaxes cholecystokinin- and KCl-induced tension in male guinea pig gallbladder strips.
abstract: Estrogen has been shown to have an inhibitory effect on the contractility of gastrointestinal smooth muscle, including the gallbladder. Since estrogen and progesterone levels are elevated during pregnancy, a biliary stasis may develop during pregnancy that is characterized by an increase in the fasting and residual volumes and by a decrease in emptying capacity. This study investigates the effect of 17β-estradiol (E2) on contraction in male guinea pig gallbladder strips. E2 induced a concentration-dependent relaxation of either CCK-induced tension or KCl-induced tension. Pretreatment of the strips with PKA inhibitor 14-22 amide myristolated had no significant effect on the E2-induced relaxation. Pretreatment of strips with 2-APB, and inhibitor of IP(3) induced Ca(2+) release, produced a significant (p<0.001) increase in the amount of E2-induced relaxation when either CCK or KCl were used to induce tension. KT5823, an inhibitor of PKG, also significantly (p<0.001) increased the amount of E2-induced relaxation. Genistein, an inhibitor of protein tyrosine kinase, had no significant effect on the E2-induced relaxation. Bisindolymaleimide IV and chelerythrine Cl- when used in combination had no significant effect on the amount of CCK-induced tension, but significantly (p<0.001) increased the amount of E2-induced relaxation. When E2 was added to the chambers prior to either CCK or KCl, a significant decrease (p<0.001) in the amount of tension generated was observed. The inhibition of extracellular Ca(2+) entry mediates the E2-induced relaxation of CCK- and KCl-induced tension in male guinea pig gallbladder strips.
authors.affiliation: University of Alberta, Department of Physiology, Edmonton, Alberta, Canada T6G 2H7. lkline@ualberta.ca
authors.forename: Loren W
authors.initials: LW
authors.lastname: Kline
authors.forename: Edward
authors.initials: E
authors.lastname: Karpinski
mesh_terms: D000818:Animals; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D019833:Genistein / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002756:Cholagogues and Choleretics; D010276:Parasympatholytics; D004958:Estradiol; D011189:Potassium Chloride; D002766:Cholecystokinin; D019833:Genistein; D011505:Protein-Tyrosine Kinases