Cytosolic calcium elevation and cGMP production induced by serotonin in a clonal cell of glial origin.
It has been shown recently that astroglial cells of the mammalian CNS possess receptors for neurotransmitters. In order to analyze what sequences of cellular events occur upon activation of these glial receptors, we utilized a 5-HT receptor in a rat clonal cell of glial origin as a model system. When the C6BU-1 glioma cells were exposed to 5-HT, the cytosolic Ca2+ concentration ([Ca2+]i) was elevated and the cellular content of cGMP was increased in a dose-dependent manner. 5-HT receptor antagonists and a Ca2+ entry blocker suppressed the increases in both [Ca2+]i and cGMP. The magnitude of the cGMP increment depended on the environmental Ca2+ concentration and was totally blocked by Ca2+ depletion. Application of a Ca2+ ionophore increased [Ca2+]i and cGMP. There was a tendency for extremely high [Ca2+]i to suppress the cGMP increment. On the contrary, membrane-permeable cyclic nucleotide analogs failed to increase [Ca2+]i. These results suggest that the following sequence of events occurs in 5-HT-induced C6BU-1 cells: activation of 5-HT receptors, Ca2+ influx, a rise in [Ca2+]i, activation of guanylate cyclase, and, finally, activation of cyclic nucleotide phosphodiesterase.
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002999:Clone Cells; D006152:Cyclic GMP / Q000096:biosynthesis*; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D015759:Ionomycin; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors
D002121:Calcium Channel Blockers; D004987:Ethers; D009712:Nucleotides, Cyclic; D012702:Serotonin Antagonists; D012701:Serotonin; D015759:Ionomycin; D006152:Cyclic GMP; D002118:Calcium