The metabolism of serotonin in neuronal cells in culture and platelets and their role in platelet aggregation

Fatima-Shad, K; Saeed, SA

The metabolism of serotonin in neuronal cells in culture and platelets and their role in platelet aggregation

Fatima-Shad, K Saeed, SA

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Publication Type:: Journal Article
Citation:: Exp Brain Res, 2007, 183 pp. 411 - 416
Issue Date:: 2007-08-08

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Field	Value	Language
dc.contributor.author	Fatima-Shad, K	en_US
dc.contributor.author	Saeed, SA	en_US
dc.date.issued	2007-08-08	en_US
dc.identifier.citation	Exp Brain Res, 2007, 183 pp. 411 - 416	en_US
dc.identifier.uri	http://hdl.handle.net/10453/34666
dc.description.abstract	The aim of this study is to find a relationship between serotonin (5-HT) and its metabolite 5-hydroxyindol acetic acid (5-HIAA) in hippocampus, frontal neocortex and platelets. Serotonin and 5-HIAA were measured in cultured neurons and compared with those produced by human platelets. The cortical neuronal 5-HIAA/serotonin ratio was 4.7 and for hippocampal neurons it was 3.2. In human platelets, this ratio was 1.35 suggesting that the highest serotonin metabolism occurs in the frontal neocortex followed by the hippocampus and platelets. In the presence of 0.3 M of p-chlorophenylalanine both cultured neurons and platelets exhibited an approximately 50% decrease in serotonin and 5-HIAA concentration suggesting similarities in the metabolic profile in both preparations. In addition, we found that serotonin by itself does not play any role in platelet aggregation but potentates this phenomenon in the presence of calcium ionophore A23187. This synergistic interaction between serotonin (2–5 M) and A23187 (0.5–2 M) was inhibited by serotonin receptor blockers [methysergide (IC50 = 18 M) and cyproheptadine (IC50, 20 M)] and calcium channel blockers (verapamil and diltiazem, IC50 = 20 and 40 M, respectively) that indicate both mechanisms are receptor mediated. Similarly, U73122, an inhibitor of phospholipase C (PLC), blocked the synergistic effect of serotonin and ionophore at an IC50 value of 9.2 M. Wortmannin, a phosphoinositide 3-kinase (PI 3-K) inhibitor, also blocked the response (IC50 = 2.6 M) by inhibiting respiratory burst. However, neither genistein, a tyrosine-speciWc protein kinase inhibitor, nor chelerythrine, a protein kinase C (PKC) inhibitor, affected aggregation. Our results are strongly suggestive of a synergistic interaction between serotonin type-2 and Ca-ionophore via a PLC/Ca signalling pathway.	en_US
dc.relation.ispartof	Exp Brain Res	en_US
dc.relation.isbasedon	10.1007/s00221-007-1133-7	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.title	The metabolism of serotonin in neuronal cells in culture and platelets and their role in platelet aggregation	en_US
dc.type	Journal Article
utslib.citation.volume	183	en_US
utslib.for	11 Medical and Health Sciences	en_US
utslib.for	17 Psychology and Cognitive Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access
pubs.consider-herdc	false	en_US
pubs.publication-status	Published	en_US
pubs.volume	183	en_US

Abstract:

The aim of this study is to find a relationship between serotonin (5-HT) and its metabolite 5-hydroxyindol acetic acid (5-HIAA) in hippocampus, frontal neocortex and platelets. Serotonin and 5-HIAA were measured in cultured neurons and compared with those produced by human platelets. The cortical neuronal 5-HIAA/serotonin ratio was 4.7 and for hippocampal neurons it was 3.2. In human platelets, this ratio was 1.35 suggesting that the highest serotonin metabolism occurs in the frontal neocortex followed by the hippocampus and platelets. In the presence of 0.3 M of p-chlorophenylalanine both cultured neurons and platelets exhibited an approximately 50% decrease in serotonin and 5-HIAA concentration suggesting similarities in the metabolic profile in both preparations. In addition, we found that serotonin by itself does not play any role in platelet aggregation but potentates this phenomenon in the presence of calcium ionophore A23187. This synergistic interaction between serotonin (2–5 M) and A23187 (0.5–2 M) was inhibited by serotonin receptor blockers [methysergide (IC50 = 18 M) and cyproheptadine (IC50, 20 M)] and calcium channel blockers (verapamil and diltiazem, IC50 = 20 and 40 M, respectively) that indicate both mechanisms are receptor mediated. Similarly, U73122, an inhibitor of phospholipase C (PLC), blocked the synergistic effect of serotonin and ionophore at an IC50 value of 9.2 M. Wortmannin, a phosphoinositide 3-kinase (PI 3-K) inhibitor, also blocked the response (IC50 = 2.6 M) by inhibiting respiratory burst. However, neither genistein, a tyrosine-speciWc protein kinase inhibitor, nor chelerythrine, a protein kinase C (PKC) inhibitor, affected aggregation. Our results are strongly suggestive of a synergistic interaction between serotonin type-2 and Ca-ionophore via a PLC/Ca signalling pathway.

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http://hdl.handle.net/10453/34666