Real-time monitoring of reduced beta-adrenergic response in fibroblasts from patients with pseudohypoparathyroidism.
The activation of cell-surface receptors usually produces a transient increase of the extracellular acidification rate in culture cells that can be detected with a biosensor-based instrument. We describe here the application of this method in monitoring hormonal response of Galphas-deficient fibroblasts from patients with pseudohypoparathyroidism type Ia (PHP-Ia). We found that following exposure to isoproterenol, the mean acidification response of fibroblasts from four PHP-Ia patients was only 18% of the response in normal cells. In contrast, these two groups of fibroblasts had similar levels of response to insulin and dibutyryl cAMP. This is the first reported experimental evidence correlating reduced Galphas activity with diminished cellular responsiveness to hormones in cultured living cells. Our results also indicate that this approach will be useful for rapid screening of other metabolic diseases caused by abnormal cellular signaling.
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Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, California, 90024, USA.
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Fung
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D003199:Computer Systems; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000494:pharmacology*; D008991:Monitoring, Physiologic / Q000379:methods*; D010084:Oxidation-Reduction; D011547:Pseudohypoparathyroidism / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D007545:Isoproterenol