Modulation of cholecystokinin activity by albumin.
We found that a variety of cholecystokinin (CCK) receptor ligands bind to bovine serum albumin (BSA). This binding was rapid, fully reversible, temperature independent, of low affinity, and specific for BSA; it depended on the concentration of BSA, the chemical structure of the ligand, and the chemical composition of the incubation medium. BSA also decreased the binding of 125I-labeled CCK octapeptide (125I-CCK-8) to CCK receptors on pancreatic acini and membranes but increased the potency with which CCK-8 inhibited binding of 125I-CCK-8. These counterintuitive findings appeared to result from BSA altering the affinities of CCK-8 for different affinity states of the pancreatic CCK receptor. An alternate hypothesis is that BSA increased the efficacy of CCK-8 such that it bound to receptors and also caused biochemical changes in other receptors that reduced their ability to bind 125I-CCK-8. BSA enhanced the ability of CCK-8 to stimulate amylase secretion from pancreatic acini and to cause contraction of dispersed gastric smooth muscle cells. Thus, CCK can bind to BSA, and the BSA-CCK complex has substantially different activities from the free, uncomplexed hormone.
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism* / Q000494:pharmacology; D020109:Devazepide; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D012844:Sincalide / Q000378:metabolism* / Q000494:pharmacology
D001570:Benzodiazepinones; D007457:Iodine Radioisotopes; D011949:Receptors, Cholecystokinin; D012710:Serum Albumin, Bovine; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide