In vitro effects of cholecystokinin fragments on human gallbladders. Evidence for an altered CCK-receptor structure in a subgroup of patients with gallstones.

BACKGROUND/AIM: This study addresses cholecystokinin (CCK)-receptor alterations in stone-diseased and stone-free human gallbladders using different CCK-fragments.

METHODS

Serosa-free muscle strips were mounted in a modified Krebs-Henseleit-solution of 37 degrees C and aerated with carbogen. The following concentrations of CCK-fragments (CCK 26-33, N-Acetyl CCK 27-33 sulf., CCK 26-29 sulf., CCK 25-33 sulf.) were achieved: 0.1 nmol, 0.5 nmol, 2 nmol, 10 nmol, 100 nmol.

RESULTS

Stone-diseased gallbladders were classified into two groups based on their in vitro reaction to CCK 26-33 (CCK-octapeptide). Muscle strips not contracting below 10 nmol were assigned to the subcontractor group. Histologically scarification, necrosis and signs of severe inflammation of the mucosa were seen in 76.9% of this group. Those starting contractions at 0.1 nmol (like the control group) were called the contractor group. This group had a shallow mucosa and mild inflammatory signs in 54.5%. The sub-contractor group showed higher spontaneous phasic activity at lower tonic activity than the contractor and control groups. In the sub-contractor group CCK 27-33 caused several times higher contractions than all other fragments. A maximal contraction level in the contractor and control groups was reached by CCK 25-33.

CONCLUSIONS

This striking effect of CCK 27-33 in the sub-contractor group favors the view of CCK-receptor structural alteration in a subgroup of patients with cholecystolithiasis.