Chromogranin A (CgA) is a member of a family of highly acidic proteins, chromogranins, which are co-stored in the adrenergic neurons and paraneurons and co-released with adrenaline and noradrenaline (NAd) in response to adequate stimulation. The present study provides novel evidence that CgA-like immunoreactivity (IR) is stored in the exocrine cells in the granular convoluted tubule, and is secreted into saliva by stimulation with NAd and acetylcholine (ACh) in the isolated and perfused rat submandibular gland. NAd at 1 microM produced maximum secretion of CgA-like IR (<< 0.9 mM) and a marked increase in salivary flow. Further increases in NAd concentration (10 or 100 microM) yielded concentration-dependent decreases in both responses. ACh at 1 microM produced maximum salivary flow and a slight elevation of CgA-like IR secretion (6 microM); 100 microM ACh decreased the salivary flow but increased the CgA-like IR secretion (0.6 mM). Electron microscopic examination showed vigorous compound exocytosis of secretory granules in the cells of the granular convoluted tubule when the submandibular gland was stimulated with 1 microM NAd. These results provide an experimental basis for the view that the salivary CgA-like IR secretion may be a sensitive and quantitative index of the activity of the sympathetic nervous system innervating the gland.
SUMMARY
Chromogranin A (CgA) is a member of a family of highly acidic proteins, chromogranins, which are co‐stored in the adrenergic neurons and paraneurons and co‐released with adrenaline and noradrenaline (NAd) in response to adequate stimulation. The present study provides novel evidence that CgA‐like immunoreactivity (IR) is stored in the exocrine cells in the granular convoluted tubule, and is secreted into saliva by stimulation with NAd and acetylcholine (ACh) in the isolated and perfused rat submandibular gland. NAd at 1 μM produced maximum secretion of CgA‐like IR (<< 0.9 mM) and a marked increase in salivary flow. Further increases in NAd concentration (10 or 100 μM) yielded concentration‐dependent decreases in both responses. ACh at 1 μM produced maximum salivary flow and a slight elevation of CgA‐like IR secretion (6 μM); 100 μM ACh decreased the salivary flow but increased the CgA‐like IR secretion (0.6 mM). Electron microscopic examination showed vigorous compound exocytosis of secretory granules in the cells of the granular convoluted tubule when the submandibular gland was stimulated with 1 μM NAd. These results provide an experimental basis for the view that the salivary CgA‐like IR secretion may be a sensitive and quantitative index of the activity of the sympathetic nervous system innervating the gland.
PC12 cells growth-arrested with bafilomycin A1 died showing apoptotic chromatin condensation in the nuclei. The bafdomycin At-induced chromatin condensation was preceded by neurite outgrowth (NOG), required higher concentrations of bafilomycin A1 than NOG, and was suppressed by cycloheximide and aurintricarboxylic acid. NH4C! (10 raM), another acidotropic pH perturbing agent, neither induced apoptotic chromatin condensation by itself nor suppressed that induced by bafilomycin A1, suggesting that bafilomycin Ai-induced apoptosis occurs independently of intracellular pH in PC12 cells.
A simple and sensitive enzyme immunoassay (EIA) was developed for determining human chromogranin A (CgA) -like immunoreactivity (IR) with use of synthetic human CgA (344-374) as antigen. In the development of the present EIA system, purposely designed N"-biotinylated glycylglycyl-human CgA (344-374), which was synthesized, was proved to be a useful biotinylated derivative. Typical standard curves ranged from 13.7 fmol/mL to 10 pmol/mL of CgA-like IR. In the present EIA, the curves for dilution of human plasma, urine, and saliva paralleled the standard curve for synthetic human CgA (344-374). The intraassay coefficient of variation for measurement of human plasma CgA was from 2.6% to 8.5%, indicating that reliable determinations can be performed for human plasma. The levels of CgA-like IR were 0.34i0.08 pmol/mL (meaniSD, n: 10) in fasting normal plasma, 0.181: 0.05 pmol/mL (n=8) in urine, and 0.1 1350.05 pmol /mL (n:8) in saliva in the morning are comparable with the respective values in RIA reported in the previous papers.
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