Exocytosis in various secretory cells is regulated by Ca2+ signaling. In this minireview, I will introduce our recent approach, which we have termed comparative biology of exocytosis, to the study of Ca2+-dependent secretion in such cells. In this approach, we quantify and compare the secretory process in different cell types (neurons, endocrine cells, and exocrine cells, with the same techniques. This approach benefits from the fact that the biochemistry and ultrastructure of these cells are relatively well characterized and it is expected to be particularly revealing because of the marked differences in the properties of exocytosis thought to exist among different secretory cells. The first part of this article deals with the mechanism by which Ca2+ signaling regulates exocytosis in exocrine cells, and the second part deals more generally with the diversity in the kinetics of the exocytotic machinery among different types of cells and secretory vesicles.
Biochemistry ; Biology ; Endocrine Cells ; Exocytosis* ; Kinetics ; Secretory Pathway ; Secretory Vesicles

We have experienced two cases of extramammary Paget's disease. The first case was a 68-year-old male who showed erythematous, crusted, oozing, eczematoid patches on the scroturn, penile root and pubic area, and verrucous plaque on the left pubic area of 5 years' duration. The second case was a 60-year-old male who showed erythematous, oozing, hyperkeratotic plaque and nodular mass on the scrotum of 4 years' duration. In electron microscopic findings of the first case, the Paget's cells was suggested to be formed by pleuripotential germinative cells; well developed microvilli, numerous electron lucent secretory granules, a few electron dense granules, apocrine type secretion and well developed desmosome.
Aged ; Desmosomes ; Humans ; Male ; Microvilli ; Middle Aged ; Paget Disease, Extramammary ; Scrotum ; Secretory Vesicles

To study tubal adhesion, tubal patency and histologic difference under light, electronic microcopy in a site of anastomosis, authors performed three anastomosis surgery in rabbit fallopian tube;1-layer and 2-layer anastomosis in splint-not-used group(group 1) and in splint-used group(group 2) and laser anastomosis in splint-used group(group 3). 10 rabbits were used in each group, therefore the total number of experimental rabbits in 3 groups were 30. The results were as follows; 1. The degree of gross adhesion in group II was significantly high as compared with other groups but there was no difference between left and right tube in the degree of adh- esion in each group(Table 1). 2. The incidence of tubal patency in group I was significantly high(89%) as compared with group I(44%). Especially, the incidence of tubal patency in group III was significantly high(100%) but there was no difference between left and right tube in incidence of tubal patency in each group. 3. Inflammatory cell infiltration appeared in each group on optical microscopic examin- ation. Especially, fibrosis and inflammatory cell infiltration appeared more in group II but there was no statistically significant difference. And there was no significant difference between left and right tube in each group. 4. Transmission electron microscopic examination of group I, as compared with normal control group, showed increase of microvilli and secretory granules and decrease in size of epithelial cell. Epithelial cell was morphologically transformed but maintained the original structure comparatively. TEM examination of group II, as compared with normal control group, showed decrease of microvilli and secretory granules and flattening of epithelial cell. It showed that epithelial cell vanished in it's original structure. TEM examination of group III, as compared with normal control group, showed decrease of microvilli and increase of secretory granules and morphological transformation of epithelial cell. Group III showed the resemblence to normal control group. From the above results, in reversal tuboplasty and tubal factor infertility, it is consi- dered that simple splint-used anastomosis or splint-used anastomosis with Nd-YAG laser will improve the successful rate of tubal anastomosis.
Epithelial Cells ; Fallopian Tubes* ; Female ; Fibrosis ; Incidence ; Infertility ; Lasers, Solid-State* ; Microvilli ; Rabbits ; Secretory Vesicles ; Splints*

To elucidate the argument on the hypertensive effect of repeated stress, morphological study on the juxtaglomerular apparatus of pain-stressed mice was carried out. Following the repeated stress on mice by subcutaneous injections of formalin every day, animals were sacrificed on 1, 3, 6, 12 hours and 1, 2, 3, 6 days after the 5th injection. Kidneys fixed in 10%, Zenker-formol solution were routinely processed, and 4um sections were stained by Bowie's stain. For the precise interpretation, following protocols were applied; Comparing the amount of secretory granules, juxtaglomerular granulation index (JGI) was weighted on every 1000 glomeruli according to their granulaities. Comparing the proportional appearance of juxtaglomerular apparatus, granulation cell index (GCI) was counted as a mean number of granular juxtaglomerular apparatus among every 100 glomeruli. Comparing the cellularities of a single juxtaglomerular apparatus, juxtaglomerular granular cell count (JGCC) was counted as a mean number of granular juxtaglomerular cells appearing in a longitudinally. sectioned afferent arteriole. Comparing the functional relationship between the juxtaglomerular cells and macula densa cells, macula densa cell count (MD count) was counted as the mean number of macular densa cells having contacts with granular juxtaglomerular cells. Result of this experiment was processed and interpreted as followings. 1. Repeated pain-stress give rise to the prominant effect to juxtaglomerular cells, as high as double granular amount as compared to normal one, during 3-6 hours after the last stress. 2. Functional relationship between the distal convoluted tubule and Juxtaglomerular cells, checked out by MD contacts, was also highest during 3 to 6 hours term. 3. The effects were decreased afterwards, but still most counts were higher than those of normal data until 6th day, the last term of this experiment. 4. Present study show that the repeated pain-stress initiate the significant pressure-rising effect to animals during the first day after the last stress, and these effects may be latent during some days afterwards. 5. As the precise mechanism involved in this aspect remains to be elucidated, further studies includingelectron microscopic and histochemical methods shall be suggested.
Animals ; Arterioles ; Cell Count ; Formaldehyde ; Injections, Subcutaneous ; Juxtaglomerular Apparatus ; Kidney ; Mice* ; Secretory Vesicles

Sperm acquires capacity of motility and fertility during the process of semen coagulation and liquefaction. The main coagulative protein is Semenogelin I (Sg I), specifically produced by seminal vesicles, and then decomposed by prostate specific antigens (PSA) in sperm liquefaction into a series of small fragments. These fragments, with a variety of physiological functions, are very important for the regulation of sperm capacity acquisition and progressive movement.
Humans ; Male ; Seminal Vesicle Secretory Proteins ; physiology ; Seminal Vesicles ; metabolism ; physiology

In pancreatic acinar cells Ca(2+)-dependent secretagogues promote the fusion of zymogen granules (ZG) with the apical plasma membrane (PM) and exocytosis of digestive enzymes. In addition to exocytotic fusion complexes between SNARE proteins in the ZG membrane (ZGM) and the apical PM, enzyme secretion elicited by Ca(2+)-dependent secretagogues requires cytosolic Cl and K+ and is inhibited by blockers of Cl- and K+-channels. We have identified a Cl-conductance activated by ATP, and a K+-conductance (with properties similar to ATP-sensitive K+-channels), regulated by the granule matrix protein Zg-16p in the ZGM. Both conductances are inversely regulated by a 65-kD mdr1 gene product. We have also identified a novel Ca(2+)-activated anion conductance in ZGM, the Ca(2+)-sensitivity of which increases 50-fold when Cl is replaced by 1. This conductance is blocked by micromolar H2-DIDS or DTT, reminiscent of a family of epithelial Ca(2+)-activated Cl -channels (CaCC). Expression of a CaCC in exocrine pancreas has been confirmed by RT-PCR analysis, and by immunoblotting and immunogold labeling of ZG membranes. These data suggest that ion channels in the ZGM are essential elements in pancreatic exocytosis.
Animal ; Chloride Channels/metabolism* ; Chloride Channels/genetics ; Exocytosis/physiology* ; Gene Expression/physiology ; P-Glycoprotein/metabolism ; P-Glycoprotein/genetics ; Pancreas/secretion* ; Pancreas/cytology ; Potassium Channels/metabolism* ; Potassium Channels/genetics ; Secretory Vesicles/secretion ; Secretory Vesicles/metabolism* ; Support, U.S. Gov't, P.H.S.

Pancreatic acinar cells exhibit a polarity that is characterized by the localization of secretory granules at the apical membrane. However, the factors that regulate cellular polarity in these cells are not well understood. In this study, we investigated the effect of Mist1, a basic helix-loop-helix transcription factor, on the cellular architecture of pancreatic acinar cells. Mist1-null mice displayed secretory granules that were diffuse throughout the pancreatic acinar cells, from the apical to basolateral membranes, whereas Mist1 heterozygote mice showed apical localization of secretory granules. Deletion of the Mist1 gene decreased the expression of type 3 inositol 1,4,5-triphosphate receptors (IP3R) but did not affect apical localization and expression of IP3R2. Mist1-null mice also displayed an increase in luminal areas and an increase in the expression of zymogen granules in pancreatic acinar cells. These results suggest that Mist1 plays a critical role in polar localization of cellular organelles and in maintaining cellular architecture in mouse pancreatic acinar cells.
Acinar Cells ; Animals ; Cell Polarity ; Heterozygote ; Inositol 1,4,5-Trisphosphate Receptors ; Membranes ; Mice ; Organelles ; Phenobarbital ; Secretory Vesicles ; Transcription Factors

BACKGROUND: Chromogranin A (CgA) is a 49-kDa glycoprotein produced by endocrine cells and is stored and secreted together with the resident hormones of electron-dense core secretory granules. Although the physiologic role of this protein is still unclear, recent data suggest that it may play a critical role in the maturation of secretory granules. This study was performed in order to evaluate the clinical significance of CgA expression in bile duct cancer. METHODS: The cases of 113 patients who underwent operations for bile duct cancer from 1986 to 1995 were reviewed for clinicopathologic characteristics, and deparaffinized sections of formalin-fixed tumor tissue samples were immunostained for CgA by using ABC method. RESULTS: Forty cases (35.4%) had tumor cells stained with CgA. Although poorly differentiated tumors (n=8) were not stained by CgA, no differences were noted in the positive rates for other clinico-pathologic characteristics, including age, sex, extent of disease, lymph-node metastasis, gross type, location of the tumor, and AJCC TNM stage. Eighty-three (83) curatively resected patients were analyzed for survival time based on clinico pathologic characteristics and CgA positivity. There was no difference in the overall survival time between the CgA positive (n=28) and negative (n=55) patients. However, in cases (stage III or IV, n=51) with lymph-node metastasis or adjacent organ invasion, patients (n=17) with a CgA- positive tumor had a significantly better prognosis than those (n=34) with a CgA-negative tumor (p=0.0318). The prognoses for the 28 cases with CgA-positive tumors did not correlate with known prognostic factors, including the TNM stage. Therefore, a CgA positive tumor may have a different tumor biology from that of a CgA negative tumor. CONCLUSIONS: Neuroendocrine differentiation in bile duct cancer is not a rare phenomenon and may be associated with a good prognosis for advanced bile duct cancer patients who have undergone a curative resection.
Bile Duct Neoplasms* ; Bile Ducts* ; Bile* ; Biology ; Chromogranin A ; Endocrine Cells ; Glycoproteins ; Humans ; Neoplasm Metastasis ; Prognosis ; Secretory Vesicles

A case of primary carcinoid tumor of the liver with striking central fibrous scar in a 61-year-old male is reported. Tumor cells contained electron dense secretory granules with an average diameter 150~200 nm which demonstrated positive immunohistochemical reaction for neuron-specific enolase, synaptophysin and chromogranin. The stellate central scar was observed in various hepatic tumors including focal nodular hyperplasia, fibrolamellar carcinoma, or sclerosing hepatocellular carcinoma, but have not been reported in carcinoid tumor.
Carcinoid Tumor* ; Carcinoma, Hepatocellular ; Cicatrix ; Focal Nodular Hyperplasia ; Humans ; Liver ; Male ; Middle Aged ; Phosphopyruvate Hydratase ; Secretory Vesicles ; Strikes, Employee ; Synaptophysin

This study was performed to investigate the subcellular changes of rat atrial muscle cells by immobilization stress. Sprague -Dawley rats weighting 200 gm were immobilized in small round plastic tube for 2, 6, 12, and 24 hours respectively. The atrial tissue obtained from each animals were observed by transmission electron microscopes. In the heart of rat subjected 2 hours immobilization stress no significant morphological changes were found in electron microscopy, similarly as in control animal. After 6 and 12 hours immobilization stress, the following electron -microscopic changes of atrial myocytes were observed at the swelling of mitochondrial matrix with disturbance in cristea, focal loss of cytoplasmic matrix, vacuoles with myeline -like structure, apoptotic changes of myocytes, focal widening of intercalated disc interspace and lysis of myofibrils. After 24 hours immobilization stress, very small sized mitochondria, similarly as small sized secretory granules and various sized granules are observed in the perinuclear region of atrial myocytes. Atrial specific granules are moved centripetally toward the central region of the atrial myocytes after immobilization stress. Above results will be aid in understanding the structures of atrium with dual function of blood circulation and endocrine, and in research of modulation of secretory granules in atrial muscle cells.
Animals ; Blood Circulation ; Cytoplasm ; Heart ; Immobilization* ; Microscopy, Electron ; Mitochondria ; Muscle Cells* ; Myelin Sheath ; Myofibrils ; Plastics ; Rats* ; Secretory Vesicles ; Vacuoles