Pancreatic stone protein (PSP; reported in 1979), pancreatitis-associated protein (PAP; 1984) and regenerating protein (Reg I;1988) were discovered independently in the fields of the exocrine (pancreatitis) and endocrine (diabetes) pancreas. Subsequent analysis revealed that PSP and Reg I are identical and PAP belongs to the same protein family. PSP/Reg I and PAP share a selective and specific trypsin cleavage site and result in insoluble fibrils (PTP, PATP). Search for a functional role of PSP had led to the idea that it might serve as an inhibitor in pancreatic stone formation and PSP was renamed lithostathine. Inhibitory effects of lithostathine in stone formation have been questioned. Evidence so far obtained can support a lithogenic role rather than a lithostatic role of PSP. PAP and its isoforms have been investigated mainly regarding responses to inflammation and stress. Reg I and its isoforms have been examined on regeneration, growth and mitogenesis in gastrointestinal neoplastic diseases as well as diabetes. Evidence obtained can be applied in the prediction of prognosis and therapy for inflammatory and neoplastic diseases.

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Pancreatic duct epithelium secretes HCO(3)(-)-rich fluid, which is dependent on cystic fibrosis transmembrane conductance regulator (CFTR). HCO(3)(-) transport across the apical membrane is thought to be mediated by both SLC26A6 Cl(-)-HCO(3)(-) exchange and CFTR HCO(3)(-) conductance. In this study we examined the relative contribution and interaction of SLC26A6 and CFTR in apical HCO(3)(-) transport. Interlobular pancreatic ducts were isolated from slc26a6 null mice. Intracellular pH (pH(i)) was measured by BCECF microfluorometry. Duct cells were stimulated with forskolin and alkalinized by acetate pre-pulse in the presence of HCO(3)(-)-CO(2). Apical HCO(3)(-) secretion was estimated from the recovery rate of pH(i) from alkaline load. When the lumen was perfused with high-Cl(-) solution, the rate of apical HCO(3)(-) secretion was increased by luminal application of CFTRinh-172 in ducts from wild-type mice but it was decreased in ducts from slc26a6 -/- mice. This suggests that slc26a6 and CFTR compensate/compete with each other for apical HCO(3)(-) secretion with high Cl(-) in the lumen. With high HCO(3)(-) in the lumen, luminal CFTRinh-172 reduced the rate of apical HCO(3)(-) secretion in both wild-type and slc26a6 -/- ducts. This suggests that HCO(3)(-) conductance of CFTR mediates a significant portion of apical HCO(3)(-) secretion with high HCO(3)(-) in the lumen.

Chronic pancreatitis is a continuing inflammatory disease characterized by irreversible morphological change and, typically, by pain and permanent impairment of function. The pathogenesis of pancreatitis, either acute or chronic, is still controversial. There have been no widely accepted concepts to provide a reasonable explanation linking the known etiological factors and the pathophysiological aspects of the disease. Alcohol is undoubtedly the major etiological factor in most countries, and the relative importance of alcohol as a cause of chronic pancreatitis ranges from 40% to 90% in various countries. As fewer than 10% of alcoholics develop chronic pancreatitis, other nutritional or genetic influences are likely to be involved in the pathogenesis of alcoholic pancreatitis. Accessory pancreas incidentally found in patients with chronic alcoholic pancreatitis does not always have the pathological findings seen in the main pancreas. Integrity of the pancreatic duct seems to be another important factor for chronic alcoholic pancreatitis. Gene mutations of the cystic fibrosis transmembrane conductance regulator (CFTR), cationic trypsinogen, and pancreatic secretory trypsin inhibitor have been investigated in idiopathic chronic pancreatitis. Molecular and cell biology research during the past few years has elucidated pathophysiological factors that are involved in the pathogenesis of chronic pancreatitis, but cannot demonstrate a common pathway between etiological factors and the pathogenesis or development of the disease.

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