Biphasic effect of phorbol myristate acetate on histamine secretion induced by compound 48/80 in rat peritoneal mast cells |
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| Authors: | Y Okano K Yamada H Takagi Y Nozawa |
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| Affiliation: | 1. Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India;2. Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA;1. Laboratory of Applied Stress Biology, Department of Botany, University of Gour Banga, Malda - 732 103, West Bengal, India;2. Department of Life Science, School of Earth, Environmental and Biological Sciences, Central University of South Bihar, Gaya, Bihar, India;3. Division of Plant Biology, Bose Institute, Kolkata, West Bengal, India;4. Department of Agronomy, Food, Natural Resources, Animals and Environment (DAFNAE), University of Padova, Viale Università, 16, 35020 Legnaro, PD, Italy;5. Faculty of Health and Sport Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8574, Japan;6. Research Laboratory for Biotechnology and Biochemistry (RLABB), PO Box 13265, Kathmandu 44600, Nepal;7. Global Research Arch for Developing Education (GRADE) Academy Pvt. Ltd., Birgunj 44300, Nepal |
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| Abstract: | Rat peritoneal mast cells which had been preincubated with phorbol myristate acetate (PMA, 100 ng/ml) for 30 sec elicited an enhanced histamine secretion induced by a potent secretagogue, compound 48/80. But a longer (5 min) preincubation with PMA followed by the agonist-stimulation induced a suppressed histamine secretion. A 5 min-PMA-pretreatment inhibited the compound 48/80-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) in [32P]-labeled cells. PMA-treatment alone for 5 min induced an activation of Ca2+-efflux monitored by 45Ca2+. The inhibition of histamine secretion induced by a 5 min-PMA-pretreatment followed by the agonist-stimulation may partly be attributed to the decreased intracellular Ca2+ concentration, [Ca2+]i, probably due to the depressed PIP2 breakdown and enhanced Ca2+-efflux. On the other hand, a 30 sec-preincubation with PMA followed by compound 48/80-stimulation induced a slight but significant increase in histamine secretion. In this case, neither breakdown of PIP2 nor Ca2+-influx was enhanced to raise the [Ca2+]i. Although we are unable to explain the mechanism for the enhancement of histamine secretion by a short (30 sec) PMA-preincubation, these results suggest that the biphasic effects of PMA on histamine secretion are mediated by intracellular Ca2+ mobilization probably via protein kinase C activation. |
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