How to measure cholecystokinin in tissue, plasma and cerebrospinal fluid

This review examines a major problem for an old hormone. Hormones are defined by the ability to reach their targets via blood. Consequently, knowledge about a hormone requires measurement of its behaviour in blood. So far, however, it has proven exceptionally difficult to measure the classical gut hormone, cholecystokinin (CCK), in circulation. The review therefore describes the premises for reliable plasma CCK measurements as compared to the premises for measurement in tissue extracts and cerebrospinal fluid. The critical plasma premises comprise equimolar quantitation of the bioactive CCK peptides in circulation (CCK-83, -58, -33, -22 and -8) without interference from homologous gastrin peptides. The latter may appear nearly impossible, because the bioactive epitopes of CCK and gastrin are almost identical, and because the plasma concentrations of gastrin are more than tenfold above those of CCK. In comparison, measurement of CCK in tissue is considerably simpler, especially in extracts of the two main production sites, the brain and jejunoileal mucosa. For cerebrospinal fluid, degradation, low levels and shortage of material constitute major problems so that the molecular nature and biological/clinical relevance of CCK measurements in CSF still remain to be settled. The review finally enlists the reports on plasma CCK measurements published so far. A multitude of different immuno- and bioassays have been used with corresponding variation in the results. The theory for different types of assays in combination with general assay experience suggest that accurate CCK measurements require radioimmunoassay technology based on high-affinity antibodies. These antibodies have to be exquisitely specific for the 0-sulfated C-terminal heptapeptide amide of CCK without binding the similar gastrin epitope. Only few of such antibodies have been raised.