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Phorbol esters enhance basal and stimulated adenylate cyclase activity in a pituitary cell line
Authors:S T Summers  M J Cronin
Institution:1. School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia;2. Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, Netherlands;3. Université de Paris, Centre of Epidemiology and Statistics (CRESS), Inserm, F 75004, Paris, France;4. Institute for Evidence-Based Healthcare, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia;5. University of Texas Health Science Center at San Antonio, San Antonio, TX, United States;6. School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Canada;7. Evidence Partners, Ottawa, Canada;8. Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa
Abstract:We reported in anterior pituitary cells that hormone stimulation of cyclic AMP levels is amplified by agents that activate protein kinase C (e.g., phorbol esters). We utilized the 235-1 pituitary cell line to explore the mechanism of this response. PGE1- and forskolin-stimulated cyclic AMP accumulation and adenylate cyclase activity are enhanced by exposing viable cells to phorbol esters. Adenylate cyclase activity in the presence of PGE1 demonstrated a biphasic stimulatory, then inhibitory response to increasing GTP concentrations; phorbol esters attenuated this inhibition. These data support the hypothesis that protein kinase C can covalently change the functional state of the adenylate cyclase holoenzyme, amplifying its response to certain hormones.
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