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

To produce milk, four secretory processes are synchronized in the alveolar cell of the mature, functional mammary gland: (1) exocytosis, (2) fat synthesis and secretion, (3) secretion of ions and water, and (4) transcytosis of immunoglubulins and other substances from the interstitial space. Milk is synthesized continuously into the alveolar lumen, where it is stored until milk removal from the breast is initiated. Prolactin mediates the central nervous system regulation of milk secretion, but its influence is modified greatly by local factors that depend on milk removal from the breast. Oxytocin mediates milk let-down by stimulating the contraction of myoepithelial cells that surround the alveoli and ducts. Lactogenesis includes all the processes necessary to go from the undifferentiated mammary gland in the early pregnant animal to full lactation sometime after parturition. The most important factors in initiation of lactogenesis stage II appear to be progesterone withdrawal. The metabolic demands of breastfeeding require an increase in maternal metabolism. Postpartum suppression of fertility is thought to be the result of an alteration in pulsatile gonadotropin releasing hormone secretion from the hypothalamus. Women who wish to ensure against pregnancy during lactation usually are advised to use other contraceptive means.
Animals ; Breast ; Breast Feeding ; Central Nervous System ; Contracts ; Dietary Sucrose ; Exocytosis ; Female ; Fertility ; Gonadotropin-Releasing Hormone ; Humans ; Hypothalamus ; Ions ; Lactation ; Mammary Glands, Human ; Milk ; Milk Ejection ; Oxytocin ; Parturition ; Postpartum Period ; Pregnancy ; Progesterone ; Prolactin ; Secretory Pathway ; Transcytosis ; Water

Trichomonas vaginalis is a flagellated protozoan parasite that causes vaginitis and cervicitis in women and asymptomatic urethritis and prostatitis in men. Mast cells have been reported to be predominant in vaginal smears and vaginal walls of patients infected with T. vaginalis. Mitogen-activated protein kinase (MAPK), activated by various stimuli, have been shown to regulate the transcriptional activity of various cytokine genes in mast cells. In this study, we investigated whether MAPK is involved in ROS generation and exocytotic degranulation in HMC-1 cells induced by T. vaginalis-derived secretory products (TvSP). We found that TvSP induces the activation of MAPK and NADPH oxidase in HMC-1 cells. Stimulation with TvSP induced phosphorylation of MAPK and p47phox in HMC-1 cells. Stimulation with TvSP also induced up-regulation of CD63, a marker for exocytosis, along the surfaces of human mast cells. Pretreatment with MAPK inhibitors strongly inhibited TvSP-induced ROS generation and exocytotic degranulation. Finally, our results suggest that TvSP induces intracellular ROS generation and exocytotic degranulation in HMC-1 via MAPK signaling.
Cell Degranulation ; Cell Line ; *Exocytosis ; Humans ; Mast Cells/*drug effects/*metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Reactive Oxygen Species/*metabolism ; Trichomonas vaginalis/*metabolism ; Virulence Factors/*metabolism

Neutrophils play a major role in host defense against microbial infection. There are some clues indicate that neutrophils may also play a role in the pathophysiology of the airway obstruction in chronic asthma. We studied the roles of intracellular calcium and GTP gamma S in the regulation of neutrophils exocytosis using pipette perfusion and membrane capacitance measurement technique in whole cell patch clamp configuration. The results showed that the membrane capacitance increase induced by calcium revealed a biphasic process. The first phase occurred when the calcium level was between 0.2-14 micromol/L with a plateau amplitude of 1.23 pF and a calcium EC50 of 1.1 micromol/L. This phase might correspond to the release of the tertiary granules. The second phase occurred when the calcium concentration was between 20-70 micromol/L with a plateau increment of 6.36 pF, the calcium EC50 being about 33 micromol/L. This phase might represent the release of the primary and secondary granules. Intracellular calcium also simultaneously increased the exocytotic rate and the eventual extent in neutrophils. On the other hand, GTP gamma S can increase the exocytotic rate in a dose-dependent manner but had no effect on the eventual extent of membrane capacitance increment (>6 pF) if the cell was stimulated for a long period (>20 min). GTP gamma S (ranging from 20 to 100 micromol/L) induced the neutrophils to release all four types of the granules at very low intracellular calcium level.
Calcium ; metabolism ; Cell Degranulation ; drug effects ; Exocytosis ; drug effects ; GTP-Binding Proteins ; metabolism ; physiology ; Guanosine Triphosphate ; analogs & derivatives ; pharmacology ; Humans ; Neutrophils ; metabolism ; physiology ; Patch-Clamp Techniques

Prurigo pigmentosa is a chronic inflammatory dermatosis characterized by reticulated erythematous papules, hyperpigmentation with severe pruritus and usually occurs in young femals around their twenties. Most cases have been reported from Japan, but only twelve cases have been reported in Korea. Histopathologic findings of erythematous papules shows spongiosis, exocytosis, liquefaction degeneration of the basal cell, perivascular lymphohistiocytic infiltration in the dermis and finally dermal fibrosis and deposit of dermal melanophages in hyperpigmented lesions. We report three cases of prurigo pigmentosa which showed various histopathologic features of early, fully-developed and late stage, respectively.
Dermis ; Exocytosis ; Fibrosis ; Hyperpigmentation ; Japan ; Korea ; Prurigo* ; Pruritus ; Skin Diseases

The eukaryotic cell is compartmentalized by a series of vesicular organelles which constitute the endocytic and exocytic transport pathways. Each vesicular compartment has distinct sets of membrane proteins, structures and functions. Despite continuous vesicular transport, each vesicular compartment maintains its structure and function by use of retention and retrieval signal for its own resident proteins. Proteins in transit along the endocytic and exocytic pathway are transported without admixing with cytoplasmic constituents by successive steps of budding from the donor vesicles, formation of intermediate transport vesicles, transport, targeting to and fusion with acceptor vesicles. Specificity and fidelity of the vesicular transport are conferred by vesicular membrane proteins and small molecular weight GTP-binding proteins of the Rab subfamily. Proteins for export are packaged into specific vesicles for their final destinations. Insertion into and retrieval from the plasma membrane of transport proteins in response to cellular stimulus are a new paradigm of cellular regulatory mechanism. Secretion of neurotransmitters, hormones and enzymes by exocytosis involves a complex set of cytosolic proteins, G-proteins, proteins on the secretory granule membrane and plasma membrane. Much progress has been recently made in identifying proteins and factors involved in the exocytosis. But the molecular interactions among identified proteins and regulatory factors are unknown and remain to be elucidated. Finally our chemiosmotic hypothesis which involves the H+ electrochemical gradient across the secretory granule membrane generated by an ATP-dependent electrogenic H(+)-ATPase as the potential driving force for fusion and release of granule contents will be discussed.
Biological Transport ; *Exocytosis ; Human ; Organelles/*metabolism ; Support, Non-U.S. Gov't

Prurigo pigmentosa is a chronic pruritic inflammatory dermaoss characterized by erythematous papules in a reticulated pattern that resolve leaving a reticulated, mottled hyperpigmentation. Most cases have been reported from Japan. Two cases of prurigo pigmentosa have been reported in Korean women. We experienced a casc of prurigo pigmentosa in a Korean man of 20 years of age. Histopathological findings of reddish papule showed exocytosis, sponsiosis, intraepidermal vesicles, hydropic degeneration of basal cells in the epidermis, and hyphohistiocytic infiltration in the upper dermis. Direct irnmunofluorescence was negetive. Therapy with dapsone, 50 mg given daily, resulted in a rerinable regression of the reddish papules. The daily dose of clapsone was reduced to 25mg; however, no new reddish, pruritic papules have appeared.
Dapsone ; Dermis ; Epidermis ; Exocytosis ; Female ; Humans ; Hyperpigmentation ; Japan ; Prurigo*

BACKGROUND: Fixed drug eruptions(FDE) are a cutaneous reaction characterized by one or more circumscribed lesions that recur at the same site in response to a given medication. OBJECTIVE: The purpose of this study was to find the clinical and histopathological characteristics of FDE and to compare early FDE with late FDE histopathologically. METHOD: We clinically investigated 54 cases of FDE that visited the department of dermatology at the Kyunghee medical center from January 1993 to December 1996. Among them, 31 patients had skin biopsies and were evaluated histopathologically on the basis of duration. RESULTS: The results were summarized as follows: 1. Development of FDE did not show any difference according to sex and was evenly distributed over all the ages. 2. The latent periods of FDE were diverse in appearance from 30 minutes to 10 days, but mostly, the skin lesions erupted within 4S hours. 3. The most common skin lesions were erythematous macules. 4. Distribution of the lesions came out as solitary: 20.4%, multiple: 79.6%. S3.7% of the multiple lesions were localized to a part of body, and 16.3% were distributed over the whole body. 5. The areas in which the eruptions developed were (in descending order): upper extremity(37.0%), hand(31.5%), trunk(24.1%), face(24.1%). 6. In most cases(68.6%), the size and the number of lesions were greater in recurrente, rather than in first attacks. 7. The histopathological findings commonly showed perivascular mononuclear cell(MNC) infiltration (100%), pigmentary incontinence(77.4%), basal hydrophic degeneration(71.0%), eosinophil infiltration in dermis(61.3%), etc. 8. The epidermal histopathological findings such as spongiosis, exocytosis of MNC, basal hydrophic degeneration, keratinocyte necrosis and subepidermal vesicles could be seen more frequently in early lesions than in late ones. CONCLUSION: In our study, we were able to obtain meaningful results based on data from the combination of clinical and histopathological investigations. This study may give help to understand the characteristics of fixed drug eruptions and to plan future studies.
Biopsy ; Dermatology ; Drug Eruptions* ; Eosinophils ; Exocytosis ; Humans ; Keratinocytes ; Necrosis ; Skin

No abstract available.
Exocytosis/physiology* ; Pancreas/secretion ; Pancreas/physiology* ; Pancreas/cytology*

No abstract available.
Animal ; Calcium Signaling/physiology* ; Exocytosis/physiology ; Pancreas/physiology* ; Pancreas/cytology