Meeting Abstract

98.5  Sunday, Jan. 6  A comparison of the effects of estrogen and progesterone on cholecystokinin and KCl-induced tension in female guinea pig gallbladder strips KLINE, L.W.*; KARPINSKI, E.; University of Alberta, Edmonton lkline@ualberta.ca

Estrogen has an inhibitory effect on the contractility of gastrointestinal smooth muscle, including the gallbladder. This study investigated the effect of 17 &beta-estradiol (E2), progesterone (P), 17-hydroxyprogesterone (17-P), and a P metabolite, 20 &alpha-hydroxyprogesterone (20-P) on contraction in female guinea pig gallbladder strips. P, 17-P, 20-P, and E2 each relaxed cholecystokinin octapeptide (CCK) induced tension; the relaxation was concentration-dependent. E2 and P had a similar effect on KCl-induced tension. When the response to E2 was compared between young female guinea pigs and guinea pigs in late pregnancy, no significant difference in the response to either 50 or 100 &microM E2 was seen; however, 10 &microM E2 caused a significant increase (p<0.05) in the relaxation in strips from pregnant guinea pigs. Treatment of the strips from young guinea pigs with PKA inhibitor 14-22 amide myristolated had no significant effect on the E2-induced relaxation. Treatment of the strips with 2-APB produced a significant (p<0.001) increase in the amount of E2-induced relaxation when either CCK or KCl were used. Neither KT5823 nor L-NMMA had a significant effect on the E2-induced relaxation. Bisindolymaleimide IV and chelerythrine Cl^– 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- and E2-induced relaxation of CCK- and KCl-induced tension in female guinea pig gallbladder strips.