Chromogranin A (CgA) belongs to the granin family of uniquely acidic secretory proteins co-stored and co-secreted with other hormones and peptides in elements of the diffuse neuroendocrine system. The granins arise from different genes and are characterized by numerous sites for post-translational cleavage into shorter peptides with postulated regulatory properties. This review is directed towards endocrine aspects of CgA and its biologically active peptides. There is ample evidence from in vitro studies of distinct effects and targets for three CgA-derived peptides, vasostatin-I, pancreastatin and catestatin. Endocrine regulations are indicated from in vivo studies, consistent with the postulated prohormone function of CgA for peptides with regulatory properties. Most of the effects fit into patterns of direct or indirect, inhibitory modulations of major functions, implicating CgA peptides in regulation of calcium and glucose metabolism, cardiovascular functions, gastrointestinal motility and nociception, tissue repair, inflammatory responses and as host defense peptides in the first phase of microbial invasions.

Catestatin (bCGA(344-364)), an endogenous peptide of bovine chromogranin A, was initially characterized for its effect on the inhibition of catecholamine release from chromaffin cells. Catestatin and its active domain (bCGA(344-358)) were identified in chromaffin cells and in secretion medium. The present study identified a potent antimicrobial activity of bCGA(344-358) in the lowmicromolar range against bacteria, fungi and yeasts, without showing any haemolytic activity. Confocal laser microscopy demonstrated penetration of the rhodaminated peptide into the cell membranes of fungi and yeasts and its intracellular accumulation. Time-lapse videomicroscopy showed arrest of fungal growth upon penetration of the labelled peptide into a fungal filament. We identified several catestatin-containing fragments in the stimulated secretion medium of human polymorphonuclear neutrophils, suggesting the N-terminal sequence of catestatin (bCGA(344-358)) (named cateslytin) as a novel component of innate immunity.

The complete amino acid sequence (703 amino acid residues) of human lactotransferrin has been determined. The location of the disulfide bridges has also been investigated. Computer analysis established internal homology of the two domains (residues 1 -338 and residues 339 -703). Each domain contains a single iron-binding site and a single glycosylation site (asparagine residues 137 and 490) located in homologous positions. Prediction of the secondary structure of the two homologous moieties of human lactotransferrin has also been performed. The present results allowed a series of comparisons to be made with human serum transferrin and hen ovotransferrin. Several years ago, short cysteic-acid containing peptides [34] and short tryptic or chymotryptic glycopeptides [35] of human lactotransferrin have been described: some of the reported results could not be corroborated later. More recently, the N-terminal sequence [36] and studies concerning two glycopeptides [37] have been published. In a previous series of investigations, we reported the cleavage of the lactotransferrin molecule with cyanogen bromide (CNBr) [38]. In 1981, seven fragments were characterized and aligned (FI, FII, FIII, FIV, FV', FVI and FVII) [21]. Only four fragments (FIII, FIV, FVI and FV') have so far been sequenced [21, 391.