[Molecular mechanism of exocytosis in neural and immune system].
Exocytosis is a common process for the secretion of physiologically active substances such as neurotransmitter, hormone, and inflammatory mediators. Exocytosis is triggered by an increase in intracellular calcium ion concentration. At the nerve terminal, voltage dependent calcium channels (VDCCs) are responsible for this calcium increase. There are several types of VDCC which are different from each other in their electro-physiological and pharmacological characteristics. In order to identify the types of VDCC at the cholinergic nerve terminal, acetylcholine (ACh) release from the electric organ synaptosomes was measured in the presence of type-specific channel blockers. At least three types of VDCC were involved in the ACh release, and N- and P/Q-type VDCC had a major contribution. Adenosine receptor A1 was coupled with N-type VDCC and had negative feedback regulation of ACh release, while A2 receptor coupled with P/Q-type VDCC enhanced the ACh release. Investigation of the inhibitory effects of antibodies from patients of autoimmune disease Lambert-Eaton syndrome on ACh release revealed that P/Q-type channel was a target for the autoantibodies. Unlike the nerve terminal, little is known about the mechanism and molecules involved in the exocytosis of immune cells. Ion channel activities of secretory granule proteins of mast cells were observed. The calcium dependency of the open probability of the channel was similar to that of histamine release from mast cells. We also showed the expression of some SNARE proteins in RBL-2H3 cells. Localization and dynamics of VAMP-7 and syntaxin-3 after antigen stimulation suggested the involvement of SNARE proteins in the exocytosis of mast cells.
Hirashima
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N
Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
D000109:Acetylcholine / Q000009:adverse effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D005089:Exocytosis; D005246:Feedback; D006801:Humans; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D008563:Membrane Lipids / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D009411:Nerve Endings / Q000166:cytology* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000502:physiology; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins
D015220:Calcium Channels; D008563:Membrane Lipids; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D018047:Receptors, Purinergic P1; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D000109:Acetylcholine; D002118:Calcium