Tryptamine Induces Phosphoinositide Turnover and Modulates Adrenergic and Muscarinic Cholinergic Receptor Function in Cultured Cerebellar Granule Cells |
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Authors: | Ryoichi Ishitani Mitsutoshi Kimura Masami Takeichi De-Maw Chuang |
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Institution: | Group on Cellular Neuropharmacology, Josai University, Sakado, Saitama, Japan;and; Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, U.S.A. |
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Abstract: | Abstract: Tryptamine dose-dependently increased phosphoinositide (PI) hydrolysis by approximately fourfold in primary cultures of rat cerebellar granule cells (EC50 = 56 µ M ). 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 4β-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 ∼0.4 and ∼2.5 m M , respectively. Pretreatment of cells with tryptamine (0.5 m M ) 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 Ca2+- and Na+-dependent PI turnover in cerebellar neurons and selectively inhibited NE- and carbachol-induced PI hydrolysis. |
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Keywords: | Tryptamine Cerebellar granule cells Phosphoinositide turnover Neuromodulator Adrenergic and muscarinic cholinergic receptors |
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