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Neurosecretory granules have been isolated from rat and guinea pig neurointermediate pituitaries and their contents have been analyzed by reverse-phase high-pressure liquid chromatography and polyacrylamide gel electrophoresis. Granule components have been compared with synthetic neurohypophysial hormones and chemically characterized neurophysins. In rat granules, oxytocin, arginine vasopressin and MSEL- and VLDV-neurophysins have been identified. In isolated guinea pig granules, only arginine vasopressin and mature MSEL-neurophysin have been found. From these results it can be concluded that both the "dibasic" cleavage between vasopressin and MSEL-neurophysin and the "monobasic" cleavage between MSEL-neurophysin and copeptin occur within the granule compartment. Previous isolation from frozen guinea pig glands of a partially processed precursor encompassing MSEL-neurophysin and copeptin suggests a two-step processing of the three-domain vasopressin precursor, each involving a distinct enzymic system.
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