Tryptamine induces phosphoinositide turnover and modulates adrenergic and muscarinic cholinergic receptor function in cultured cerebellar granule cells.
Tryptamine dose-dependently increased phosphoinositide (PI) hydrolysis by approximately fourfold in primary cultures of rat cerebellar granule cells (EC50 = 56 microM). The PI response stimulated by tryptamine was dependent on the presence of extracellular Ca2+ and Na+. Tryptamine-induced PI breakdown could be partially inhibited by pretreatment with 4 beta-phorbol 12-myristate 13-acetate but not pertussis toxin. The presence of tryptamine markedly attenuated PI responses induced by norepinephrine (NE) and carbachol, with no apparent effect on the responses to 5-hydroxytryptamine and glutamate. The inhibition of NE- and carbachol-induced PI turnover by tryptamine was dose dependent with IC50 values of approximately 0.4 and approximately 2.5 mM, respectively. Pretreatment of cells with tryptamine (0.5 mM) also attenuated NE- and carbachol-induced PI turnover, but failed to affect 5-hydroxytryptamine- and glutamate-induced responses. Furthermore, ketanserin, atropine, and prazosin did not have any effect on inositol phosphate formation induced by tryptamine. These observations indicate that tryptamine markedly increased Ca(2+)- and Na(+)-dependent PI turnover in cerebellar neurons and selectively inhibited NE- and carbachol-induced PI hydrolysis.
Group on Cellular Neuropharmacology, Josai University, Saitama, Japan.
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Ishitani
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Kimura
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Takeichi
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Chuang
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D006868:Hydrolysis; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium; D014363:Tryptamines / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010716:Phosphatidylinositols; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D014363:Tryptamines; D010566:Virulence Factors, Bordetella; D014316:Tritium; C030820:tryptamine; D002217:Carbachol; D012964:Sodium; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine