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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Venter, J. C. Owicki, J. C. Kercso, K. M. Fraser, C. M. Mcconnell, H. M. Parce, J. W. Muir, V. C. Sigal, G. B. |
| Description | Author Affiliation: Owicki JC ( Molecular Devices Corp., Menlo Park, CA 94025.); |
| Abstract | Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular metabolic rates. Changes in cell metabolism were monitored continuously with a previously described silicon-based microphysiometer that detects small changes in extracellular pH. The amplitude and kinetics of the metabolic changes depend upon several factors including pretreatment of the cells prior to receptor stimulation, the dose of hormone/neurotransmitter used, and the receptor complement of the cells. Responses are receptor specific; cells transfected with receptor genes respond only to the appropriate hormone/transmitter, whereas control (nontransfected) cells or cells transfected with different receptors exhibit no response. The specificity of the responses was further documented by using pharmacological antagonists. In Chinese hamster ovary (CHO) cells transfected with human beta 2-adrenergic receptors, isoproterenol produces a 20-60% increase in the rate of extracellular acidification with an EC50 of 4 nM, a response that is competitively antagonized by (-)-propranolol. The EC50 for the isoproterenol response is shifted from 4 nM to 100 nM in the presence of 3 nM (-)-propranolol. The kinetics of the metabolic response induced by beta-adrenergic receptor stimulation are markedly slower than those elicited by muscarinic receptor agonists. The maximal metabolic response in cells transfected with beta-adrenergic receptors peaks at approximately 12 min as compared with less than 30 sec in cells transfected with muscarinic receptors, perhaps reflecting activation of different second-messenger pathways. These findings illustrate an alternative means of studying cellular responses to hormones and neurotransmitters and suggest that metabolic changes will be generally useful for detecting the consequences of receptor-ligand interactions. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 10 |
| Volume Number | 87 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1990-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Epidermal Growth Factor Pharmacology Keratinocytes Metabolism Receptors, Adrenergic, Beta Receptors, Muscarinic Transforming Growth Factors Animals Carbachol Cell Line Cells, Cultured Hydrogen-Ion Concentration Isoproterenol Drug Effects Kinetics L Cells (Cell Line) Mice Genetics Transfection Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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