Biochemistry of the chromogranin A protein family.

The secretory granules of adrenal medullary chromaffin cells synthesize, store and then liberate catecholamines by exocytosis after cell stimulation with acetylcholine, itself liberated from the splanchnic nerve (for review, see Viveros, 1975). Apart from adrenaline and noradrenaline, chromaffin granules contain a great number of molecules, essentially proteins, which are co-secreted with the catecholamines. The soluble acidic proteins of chromaffin granules have been collectively called chromogranins (Blaschko et al., 1967). Chromogranin A (CGA) is the major protein, representing 40% ofthe soluble protein ofbovine adrenal medullary chromaffin granules (Winkler, 1976). Since it was first characterized about 20 years ago (Helle, 1966), CGA has been much studied. Its physicochemical properties have been analysed in detail. However, it was only in 1986 that two independent groups obtained for the first time the complete primary sequence of CGA of the bovine chromaffin granule (Benedum et al., 1986; Iacangelo et al., 1986). The recent discovery of a negative feedback control of insulin (Tatemoto et al., 1987) and catecholamine (Simon et al., 1988) release by peptide derivatives of CGA and the presence of an anti-CGA immunoreactivity in numerous endocrine and nervous tissues, support the concept that this protein might have