Age-related changes in gallbladder contractility and gallbladder cholecystokinin receptor population in the guinea pig

We have examined the effects of aging on guinea pig biliary motility both in vitro and in vivo. The first experiment compared contractile tension of gallbladder strips from young adult (6-12 months old) and 3-year-old guinea pigs in vitro. Contraction of gallbladder strips from the young guinea pigs was twice as forceful and was more sensitive to octapeptide of cholecystokinin (CCK-8) stimulation than the gallbladder strips from the older guinea pigs. The two groups were also studied in vivo by measuring changes in the intraluminal pressure of the gallbladder in response to exogenously administered doses of CCK-8. Young adult guinea pigs were more sensitive to CCK-8 at the lower doses tested and demonstrated gallbladder constractions that were more forceful than that of the old guinea pigs. CCK receptors were measured on gallbladder muscularis membranes from young adult and old guinea pigs. The number of receptors on gallbladder membranes decreased with age: 65.0±17.7 fmoles/mg protein on membranes from 1 year old; 7.9±2.0 fmoles/mg protein on membranes from 3 years old. The binding affinity of CCK receptors on gallbladder muscularis membranes for binding to CCK-8 was not significantly different in the two age groups studied. We conclude that age-related decreases in gallbladder responses to CCK-8 may be due to decreased concentrations of CCK receptors on gallbladder muscle cells.