Changes in element concentrations induced by agonist in pig pancreatic acinar cells

Abstract

Changes in electrolytes of pig pancreatic acinar cells following application of gastrin-cholecystokinin (CCK) were investigated using the technique of X-ray microanalysis of hydrated and dehydrated sections of freshly frozen pancreas. After stimulation by CCK (10(-9) M), Na and Cl increased significantly in the cytoplasm [Na, from 10 mmol/kg wet wt. (48 mmol/kg dry wt.) to 19 mmol/kg (95 mmol/kg); Cl, from 22 mmol/kg (105 mmol/kg) to 49 mmol/kg (245 mmol/kg)] as well as in the luminal interspace [Na, from 53 mmol/kg (189 mmol/kg) to 65 mmol/kg (283 mmol/kg); Cl, from 65 mmol/kg (232 mmol/kg) to 102 mmol/kg (443 mmol/kg)]. In the secretory granules Cl increased significantly from 30 mmol/kg (86 mmol/kg) to 67 mmol/kg (203 mmol/kg). K decreased significantly from 120 mmol/kg (571 mmol/kg) to 81 mmol/kg (405 mmol/kg) in the cytoplasm, while both increased from 38 mmol/kg (109 mmol/kg) to 58 mmol/kg (176 mmol/kg) in the granules and from 46 mmol/kg (164 mmol/kg) to 48 mmol/kg (209 mmol/kg) in the luminal interspace. Ca increased significantly in the cytoplasm as well as in the luminal interspace, and decreased significantly in the secretory granules. CCK evoked Ca release from secretory granules in the secretory pole of acinar cells. The values were measured from dehydrated sections, and agreed well with those from hydrated sections. The effect of furosemide, an inhibitor of the Na+-K+-2Cl- co-transporter, on the ion transport of acinar cell was studied. When furosemide (10(-5) M) was added to the external solution, the cytoplasmic Cl and Ca concentrations decreased significantly, while there was a little decrease in Na and K concentrations under the secretory condition. These results indicate that Na+-K+-2Cl- co-transport, and Na+, Cl- and K+ exits into the lumen are involved in the mechanism of ion secretion in pig pancreatic acinar cells.

Pancreatic protease activation by alcohol metabolite depends on Ca 2+ release via acid store IP 3 receptors

“…IP 3 releases Ca 2ϩ from isolated ZGs, as well as ZGs in intact cells, whereas specific ER Ca 2ϩ pump inhibition with TG cannot liberate Ca 2ϩ from these organelles (17,36).…”

“…Important stores, from which Ca 2ϩ can be mobilized, have also been demonstrated in lysosomes and endosomes (17)(18)(19)(20)(21)(36)(37)(38)(39). Trypsin activation takes place in acid Baf-sensitive postexocytotic endocytic structures, which are, at least partially, co-localized with lysosomes (8).…”

Calcium-dependent enzyme activation and vacuole formation in the apical granular region of pancreatic acinar cells

“…The vast amount of Ca 2ϩ normally bound inside the granules (12) therefore plays an important role in making the proteins combine to osmotically and chemically inactive aggregates (33). CCK hyperstimulation liberates Ca 2ϩ from granules in intact acinar cells (34), and this could increase [Ca 2ϩ ] i close to the cytosolic face of the granule membrane, potentially opening Ca 2ϩ -activated K ϩ channels (29). There is a K ϩ conductance pathway in the ZG membrane (35) that is regulated by a high-affinity dihydropyridine-binding protein (36).…”

Glucagon-Like Peptide-1 Synthetic Analogs: New Therapeutic Agents for Use in the Treatment of Diabetes Mellitus

“…GLP-1 has been reported to inhibit ATP-sensitive K + channels (K-ATP) [87][88][89] and to facilitate the opening of voltage-dependent Ca 2+ channels (VDCCs) [3]. Intracellular Ca 2+ release channels are also targeted by GLP-1 in a cAMPdependent manner [74,90,91]. They include the type-2 isoform of ryanodine receptor (RYR-2) Ca 2+ release channels located on the endoplasmic reticulum.…”

“…This is also true for GLP-1 receptors expressed on pancreatic β-cells. By stimulating production of cAMP, GLP-1 acts as a modulator of the β-cell glucose signaling system (Fig.2) [74,90,91]. They include the type-2 isoform of ryanodine receptor (RYR-2) Ca 2+ release channels located on the endoplasmic reticulum.…”