A comparison of the effects of various sex steroids on cholecystokinin- and KCl-induced tension in female guinea pig gallbladder strips

Estrogen (E) has been shown to have an inhibitory effect on the contractility of gastrointestinal smooth muscle, including the gallbladder. During pregnancy E and progesterone (P) levels are elevated. 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 17 beta-estradiol (E2), dihydrotestosterone (DHT), P, 17-hydroxyprogesterone (17-P), and a P metabolite, 20 alpha-hydroxyprogesterone (20-P) on contraction in female guinea pig gallbladder strips. DHT, P, 17-P, 20-P, and E2 each induced a concentration-dependent relaxation of cholecystokinin octapeptide (CCK) induced tension. DHT, E2, and P also induced a concentration-dependent relaxation of KCl-induced tension. When the response to E2 was compared to strips from young female guinea pigs with those taken from guinea pigs in late pregnancy, there was no significant difference in the response to either 50 or 100 mu M E2; however, 10 mu M E2 caused a significant increase (p < 0.05) in the amount of relaxation in strips from pregnant guinea pigs. Treatment of the strips from young guinea pigs with PICA inhibitor 14-22 amide myristolated had no significant effect on the E2-induced relaxation. Treatment of the strips with 2-APB, an inhibitor of IP3 induced Ca2+ release, produced a significant (p < 0.001) increase in the amount of E2-induced relaxation when either CCK or KCl were used. Neither KT5823, a PKG inhibitor, nor L-NMMA, a nitric oxide (NO) synthase inhibitor, had a significant effect on the E2-induced relaxation. Bisindolymaleimide IV and chelerythrine Cl-, PKC blockers, were used in combination with no significant effect on the amount of CCK-induced tension, but significantly (p < 0.01) increased the amount of E2-induced relaxation. When either E2 or P were added to the chambers 3 min prior to either CCK or KCl, a significant decrease (p < 0.001) in the amount of tension generated was observed. The inhibition of extracellular Ca2+ entry mediates both P-induced and E2-induced relaxation of CCK- and KCl-induced tension in female guinea pig gallbladder strips. (C) 2013 Elsevier Inc. All rights reserved.