In vitro effects of cholecystokinin fragments on human gallbladders. Evidence for an altered CCK-receptor structure in a subgroup of patients with gallstones.
OBJECTIVE
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.
Schneider
H
H
Department of General Surgery, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
Sänger
P
P
Hanisch
E
E
D000328:Adult; D000368:Aged; D002769:Cholelithiasis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005704:Gallbladder / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D011949:Receptors, Cholecystokinin / Q000235:genetics*; D012016:Reference Values; D012844:Sincalide / Q000494:pharmacology*
D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; D012844:Sincalide