Agonist-specific calcium signaling and phosphoinositide hydrolysis in human SK-N-MCIXC neuroepithelioma cells.
Fura-2 digital imaging microfluorimetry was used to evaluate the Ca2+ signals generated in single clonal human neuroepithelioma cells (SK-N-MCIXC) in response to agonists that stimulate phosphoinositide hydrolysis. Addition of optimal concentrations of either endothelin-1 (ET-1), ATP, oxotremorine-M (Oxo-M), or norepinephrine (NE) all resulted in an increase in the concentration of cytosolic calcium (Ca2+i) but of different magnitudes (ET-1 = ATP > Oxo-M > NE). The Ca2+ signals elicited by the individual agonists also differed from each other in terms of their latency of onset, rate of rise and decay, and prevalence of a sustained phase of Ca2+ influx. The Ca2+ signals that occurred in response to ATP had a shorter latency and more rapid rates of rise and decay than those observed for the other three agonists. Furthermore, a sustained plateau phase of the Ca2+ signal, which was characteristic of the response to Oxo-M, was observed in < 40% of cells stimulated with ET-1 and absent from Ca2+ signals elicited after NE addition. Removal of extracellular Ca2+ enhanced the rate of decay of Ca2+ signals generated by ATP, ET-1, or Oxo-M and, when evident, abolished the sustained phase of Ca2+ influx. In the absence of extracellular Ca2+, NE elicited asynchronous multiple Ca2+ transients. In either the absence or presence of extracellular Ca2+-, > 94% of cells responded to ET-1 or ATP, whereas corresponding values for Oxo-M and NE were approximately 74 and approximately 48%.(ABSTRACT TRUNCATED AT 250 WORDS)
Neuroscience Laboratory, Mental Health Research Institute, Ann Arbor, Michigan 48104-1687.
R K
RK
Palmer
D I
DI
Yule
E L
EL
McEwen
J A
JA
Williams
S K
SK
Fisher
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured
D016232:Endothelins; D010716:Phosphatidylinositols; D010095:Oxotremorine; C042743:oxotremorine M; D000255:Adenosine Triphosphate; D002118:Calcium; D009638:Norepinephrine