The nonselective cation channel in the basolateral membrane of rat exocrine pancreas

Nonselective Ca²⁺-sensitive cation channels in the basolateral membrane of isolated cells of the rat exocrine pancreas were investigated with the patch clamp technique. With 1.3 mmol/l Ca²⁺ on the cytosolic side, the mean openstate probabilityP _o of one channel was about 0.5. In insideout oriented cell-excised membrane patches the substances diphenylamine-2-carboxylic acid (DPC), 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and 3,5-dichlorodiphenylamine-2-carboxylic acid (DCDPC) were applied to the cytosolic side. These compounds inhibited the nonselective cation channels by increasing the mean channel closed time (slow block). 100 mol/l of NPPB or DPC decreasedP _o from 0.5 (control conditions) to 0.2 and 0.04, respectively, whereas 100 mol/l of DCDPC blocked the channel completely. All effects were reversible. 1 mmol/l quinine also reducedP _o, but in contrast to the abov mentioned substances, it induced fast flickering. Ba²⁺ (70 mmol/l) and tetraethylammonium (TEA⁺; 20 mmol/l) had no effects. We investigated also the stilbene disulfonates 4-acetamido-4-isothiocyanatostilbene-2,2-disulfonic acid (SITS), 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS) and 4,4-dinitro-2,2-stilbenedisulfonate (DNDS). 10 mol/l SITS applied to the cytosolic side increasedP _o from 0.5 to 0.7 and with 100 mol/l SITS the channels remained nearly permanently in its open state (P _o1). A similar activation of the channels was also observed with DIDS and DNDS. These effects were poorly reversible. The stilbene disulfonates acted by increasing the channel mean open time. When the channel was inactivated by decreasing bath Ca²⁺ concentration to 0.1 mol/l, addition of 100 mol/l of SITS had no effect. Similarly, reducing bath Ca²⁺ concentration from 1.3 mmol/l in presence of 100 mol/l SITS (channels are maximally activated) to 0.1 mol/l, inactivated the channels completely. These results demonstrate, that SITS can only activate the channels in the presence of Ca²⁺. SITS had no effects, when applied to the extracellular side in outside out patches. In summary, the substances DPC, NPPB and DCDPC inhibit nonselective cation channels, where DCDPC has the most potent and NPPB the smallest effect; whereas SITS, DIDS and DNDS activate the channel when applied from the cytosolic side in the presence of Ca²⁺ ions.     

Cystic neoplasms of the exocrine pancreas

The increasing use of radiological imaging has led to greater detection of small and asymptomatic cystic lesions of the pancreas. Most are resectable, but not all are neoplastic. This review provides an update on the histopathology, immunohistochemistry, molecular biology, pathogenesis and management of cystic neoplasms of the exocrine pancreas. These include the serous, the mucinous cystic, the intraductal papillary mucinous and the solid pseudopapillary neoplasms. Recently reported variants are described and very rare cystic variants of other pancreatic epithelial and mesenchymal neoplasms are briefly mentioned.     

The ultrastructural histochemistry of the basement membranes of the exocrine pancreas

The basement membranes in the exocrine pancreas were examined by routine electron microscopy, by fixation for electron microscopy with a glutaraldehyde-tannic acid solution and by staining for ultrastructural demonstration of mucosubstances with the dialyzed iron, high iron diamine, ruthenium red and Concanavalin A-horseradish peroxidase procedures. The basement membranes are considered from morphologic and histochemical observations to consist of an inner lamina lucida, an intermediate lamina densa and an outer lamina diffusa. Sulfated mucosubstance was found in the lamina diffusa of the basement membrane of all epithelial cells and capillary endothelial cells but was encountered in the lamina lucida of the duct cells exclusively. Bridging structures, presumably polypeptides, were also seen connecting the lamina densa and the basal plasma membrane in specimens fixed with the glutaraldehyde-tannic acid solution. The findings demonstrated that the histochemical and morphological qualities of the basement membrane are uniform for a given cell type but differ considerably among the several cell types in the pancreas.     

Anastomosing tubular arrangement of the exocrine pancreas

Wax reconstructions of zymogen-containing cells in rat show the arrangement of the exocrine pancreas to be a branching, anastomosing system of tubules which vary in diameter and end blindly. This arrangement is not that of a true acinar gland.     

Argyrophil cells in the exocrine pancreas.

The silver positive cells of the exocrine pancreas and primary pancreatic cancers were studied with the Grimelius silver stain and the Fontana-Masson technique. In the pancreas, cells containing black granules with the Grimelius method, which at the same time react negative to Fontana-Masson, are considered argyrophil. These cells were present in the basal portion of some of the acinar tissue and in the ductal epithelia, as well as in the A cells of islets. The incidence and distribution of these argyrophil cells were also studied in a variety of ductal lesions. In the so-called ductal proliferation numerous numbers of positive cells were found. Argyrophil cells were frequently situated in the basal portion of ductal squamous cell metaplasia. In goblet cell metaplasia the numbers were few, and less than in normal ducts. We concluded that the distribution and incidence of argyrophil cells in the ductal epithelia is related to chronic pancreatitis, and in particular to regenerative processes. The incidence of argyrophil cells in primary pancreatic cancer, excluding islets cell origin, was 18 per 41 cases (43.4%). We considered them pancreatic cancer with argyrophil cells.     

The ultrastructural histochemistry of the basement membranes of the exocrine pancreas.

The basement membranes in the exocrine pancreas were examined by routine electron microscopy, by fixation for electron microscopy with a glutaraldehyde-tannic acid solution and by staining for ultrastructural demonstration of mucosubstances with the dialyzed iron, high iron diamine, ruthenium red and Concanavalin A-horseradish peroxidase procedures. The basement membranes are considered from morphologic and histochemical observations to consist of an inner lamina lucida, an intermediate lamina densa and an outer lamina diffusa. Sulfated mucosubstance was found in the lamina diffusa of the basement membrane of all epithelial cells and capillary endothelial cells but was encountered in the lamina lucida of the duct cells exclusively. Bridging structures, presumably polypeptides, were also seen connecting the lamina densa and the basal plasma membrane in specimens fixed with the glutaraldehydetannic acid solution. The findings demonstrated that the histochemical and morphological qualities of the basement membrane are uniform of a given cell type but differ considerably among the several cell types in the pancreas.     

Acinar cell neoplasms of the exocrine pancreas.

The pathological features of 12 acinar cell neoplasms of the pancreas are described; these comprise 11 carcinomas, of which seven were pure acinar cell growths and four were mixed acinar and ductal carcinomas, and one adenoma. These tumors occurred in a series of 105 during the period 162-75. Thrombotic endocarditis developed in three out the 11 carcinoma cases. The distinctive histological features of these neoplasms and the means of differentiating them from anaplastic carcinomas and certain other carcinomas, for example, islet cell carcinoma, oat cell carcinomas, and carcinoid tumours, are discussed. The poor prognosis of pancreatic cancers is emphasized, and reasons are put forward for believing that future epidemiological studies may need to take account of the histological types of pancreatic carcinoma.     

The fine structure of the exocrine pancreas of the mink (author's transl)]

The pancreas of female mink has been investigated by transmission electron microscopic means. The following results can be summarized: The pancreas of the mink is built up by the well known gland lobules as found in many other species; each lobule contains branched ducts with acini. The acinar cells are characteristically packed with granular endoplasmic reticulum, large Golgi apparatuses, and zymogen granules. Particularly interesting are large vacuoles, which seem to emerge directly from the endoplasmic reticular cysternae. The centroacinar cells form relatively extended protrusions or pseudopodia, which frequently penetrate into the intercellular spaces between neighbouring acinar cells. The peripheral isthmic parts of the ducts are covered by an isoprismatic epithelium. The adventitial tissue of the intralobular ducts contain mucous glands. Within the loose connective tissue between the exocrine cells, blood vessels as well as numerous nerves can be found. These results are compared to earlier reports on the same subject, and are also discussed together with available data from the literature.     

Histochemical localization of carbonic anhydrase in the pig's exocrine pancreas

Carbonic anhydrase is essential for the pancreatic secretion of NaHCO3. To localize the distribution of carbonic anhydrase in the exocrine gland and, hence, identify the potential cellular source of secreted NaHCO3, histochemical staining of carbonic anhydrase was carried out on pancreatic biopsies obtained from six pigs at both supramaximal intravenous secretin stimulation and at secretory rest. Tissue staining, using Hansson's technique, revealed a strong staining both in membranes and cytoplasm in the duct cells and a weaker cytoplasmic staining in the acinar cells. Staining reaction was abolished by 10(-5) mol l-1 acetazolamide. Duct cells, accordingly, seem to be responsible for NaHCO3 secretion, while acinar cells appear unlikely to contribute substantially to NaHCO3 secretion.