Isolation, structure and biological activity of two cholecystokinin octapeptides from sheep brain

SEVERAL peptides-for example, substance P and neurotensin-are now known to occur in both endocrine cells of the gut and in central or peripheral neurones¹. The significance of this dual distribution is far from fully understood, but it seems possible that the same peptide might function as both hormone and neurotransmitter. Vanderhaeghen et al. have reported that radioimmunoassays (RIA) for the antral hormone gastrin have shown activity in extracts of brain, particularly cerebral cortex, of a wide range of vertebrate species². However, gastrin has the same COOH-terminal pentapeptide sequence as the intestinal hormone cholecystokinin (CCK) and antisera specific for the COOH terminus of gastrin usually cross-react to some extent with CCK also. We found that the pattern of cross-reactivity of boiling water extracts of brain with six different antisera resembled that of a COOH-terminal fragment of CCK more closely than gastrin, and gel filtration studies have indicated that the main component in the extracts was compatible with the COOH-terminal octapeptide of CCK (CCK8)³; these findings have since been confirmed by others^4-6. We have purified from sheep brain two octapeptides corresponding to the CCK-like component previously identified by RIA, and report here the isolation, sequence and some properties of these molecules.