Anti-alpha-fodrin inhibits secretion from permeabilized chromaffin cells

Chromaffin cells release catecholamine- and peptide-containing granules by exocytosis, by a mechanism involving movement of secretory granules towards the cell membrane, their apposition to it and the fusion of the granule membrane with the plasma membrane. One of the two subunits of membrane-associated brain spectrin, alpha-fodrin is an actin-binding protein which is found at the periphery of chromaffin cells and may be involved in secretion. Because cultured chromaffin cells can be permeabilized with detergents, giving pores large enough to permit the entry of immunoglobulin molecules, we used permeabilized cells to test the effect of specific antibodies on secretory mechanisms. Incubation of permeabilized cells with polyclonal immunoaffinity-purified monospecific anti-alpha-fodrin antibody or its Fab fragments did not modify basal release but did specifically inhibit Ca2+-induced catecholamine release by exocytosis. Our observations indicate that fodrin and the cytoskeleton participate in the release mechanism.     

Inhibition of histamine secretion from mast cells

Histamine secretion from mast cells may be inhibited by elevated intracellular levels of cyclic AMP and by several anti-allergic drugs. These compounds are claimed to act directly on the calcium-gating mechanism activated by the anaphylactic reaction, preventing influx of Ca2+ from the external environment and so blocking exocytosis. To examine this hypothesis further, we have compared here the histamine secretion induced by immunoglobulin E-directed ligands in the presence and absence of added calcium and by the ionophore A23187. Exocytosis evoked by these former agents was originally considered to be almost totally dependent on extracellular calcium but recent studies have shown otherwise. In the absence of added cation, the agents act by mobilizing membrane-bound or intracellular stores of calcium. We show that here that a variety of anti-allergic drugs are potent inhibitors in the conditions used, suggesting that alternative explanations for their action must be sought.     

Quantal transmitter secretion from myocytes loaded with acetylcholine.

It is well known that transmitter secretion requires specialized secretory organelles, the synaptic vesicles, for the packaging, storage and exocytotic release of the transmitter. Here we report that when acetylcholine (ACh) is loaded into an isolated Xenopus myocyte, there is spontaneous quantal release of ACh from the myocyte which results in activation of its own surface ACh channels and the appearance of membrane currents resembling miniature endplate currents. This myocyte secretion probably reflects Ca(2+)-regulated exocytosis of ACh-filled cytoplasmic compartments. Furthermore, step depolarization of the myocyte membrane triggers evoked ACh release from the myocyte with a weak excitation-secretion coupling. These findings suggest that quantal transmitter secretion does not require secretory pathways unique to neurons and that the essence of presynaptic differentiation may reside in the provision of transmitter supply and modification of the preexisting secretion pathway.     

Motion speed modulates walking direction discrimination: The role of the feet in biological motion perception

The human visual system is tuned to the motions of biological entities, which provide potentially vital information for survival. The current study examines the interplay between motion speed and motion direction perception. Following a brief presentation of a point-light walker walking straight ahead or slightly leftward or rightward, observers were asked to quickly judge the walking direction (left or right). Participants showed better direction discrimination when the walker walked at a fast pace compared to a natural or slow pace, and this was not simply due to a difference in motion cycles. Moreover, walking direction sensitivity could be enhanced by increasing the feet motion speed alone, so long as the direction of feet movement was consistent with that of the other body parts. These findings demonstrate that our perception of walking direction is influenced by local motion speed, and highlight the role of the feet in biological motion perception.     

Monitoring the secretion from single cells with temporal and spatial resolution

The secretion from cells plays a significant role in life activites and in the fields of neurobiology, cell biology, clinic, pathology, pharmacology etc. Thus to investigate the secretion at the single cell level with the developing methods is a frontier cross-discipline research activity. The contents, methods and new progress of this research have been reviewed by electrochemical monitoring combined with patch-clamp techniques, fluorescent detection and immunoassay, and the prospects on the frontier of the research area have been discussed.     

Monitoring the secretion from single cells with temporal and spatial resolution

The secretion from cells plays a significant role in life activites and in the fields of neurobiology, cell biology, clinic, pathology, pharmacology etc. Thus to investigate the secretion at the single cell level with the developing methods is a frontier cross-discipline research activity. The contents, methods and new progress of this research have been reviewed by electrochemical monitoring combined with patch-clamp techniques, fluorescent detection and immunoassay, and the prospects on the frontier of the research area have been discussed.     

Cytosolic Ca2+ gradients triggering unidirectional fluid secretion from exocrine pancreas.

Exocrine gland cells secrete Cl(-)-rich fluid when stimulated by neurotransmitters or hormones. This is generally ascribed to a rise in cytosolic Ca2+ concentration ([Ca2+]i), which leads to activation of Ca2(+)-dependent ion channels. A precise understanding of Cl- secretion from these cells has been hampered by a lack of knowledge about the spatial distribution of the Ca2+ signal and of the Ca2(+)-dependent ion channels in the secreting epithelial cells. We have now used the whole-cell patch-clamp method and digital imaging of [Ca2+]i to examine the response of rat pancreatic acinar cells to acetylcholine. We found a polarization of [Ca2+]i elevation and ion channel activation, and suggest that this comprises a novel 'push-pull' mechanism for unidirectional Cl- secretion. This mechanism would represent a role for cytosolic Ca2+ gradients in cellular function. The cytosolic [Ca2+]i gradients and oscillations of many other cells could have similar roles.     

Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40

Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue. Insulin is secreted from pancreatic beta cells in response to elevated plasma glucose, with various factors modifying its secretion. Free fatty acids (FFAs) provide an important energy source as nutrients, and they also act as signalling molecules in various cellular processes, including insulin secretion. Although FFAs are thought to promote insulin secretion in an acute phase, this mechanism is not clearly understood. Here we show that a G-protein-coupled receptor, GPR40, which is abundantly expressed in the pancreas, functions as a receptor for long-chain FFAs. Furthermore, we show that long-chain FFAs amplify glucose-stimulated insulin secretion from pancreatic beta cells by activating GPR40. Our results indicate that GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs.     

慢性鼻窦炎鼻分泌物中嗜酸粒细胞阳离子蛋白的表达及临床意义

目的:探讨慢性鼻窦炎(chronic rhinosinusitis,CRS)患者鼻分泌物中嗜酸粒细胞阳离子蛋白(eosinophilic cationic protein,ECP)的表达及临床意义.方法:取36例CRS患者及20例健康人鼻分泌物,用免疫荧光分析法定量检测其ECP含量.结果:CRS患者鼻分泌物ECP质量浓...