Biomaterial Database

Changes in extracellular 5-HIAA concentrations as measured by in vivo microdialysis technique in relation to changes in 5-HT release. 2004

Carina Stenfors, and Svante B Ross

Bioscience, Local Discovery, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden. carina.stenfors@astrazeneca.com

BACKGROUND The cerebral microdialysis technique has been widely used to monitor the release of 5-hydroxytryptamine (5-HT). The extracellular concentration of 5-HT has generally been shown to change after pharmacological manipulation as expected. Extracellular levels of the metabolite, 5-hydroxyindoleaceticacid (5-HIAA) does not always change in the same direction as 5-HT and has therefore generally been thought to be of no interest as a marker for 5-HT release. OBJECTIVE The aim of the present review is to analyse the connection between changes in extracellular levels of 5-HT and 5-HIAA evoked by various pharmacological means. METHODS Literature on in vivo microdialysis studies measuring extracellular 5-HT and 5-HIAA has been analysed with special attention to the great importance of the 5-HT re-uptake mechanism in determining their extracellular concentrations. RESULTS When the 5-HT reuptake mechanism is intact changes in extracellular levels of 5-HT and 5-HIAA go in the same directions, e.g decrease after compounds that decrease 5-HT release and increase after compounds that enhance 5-HT release. Because the extracellular 5-HIAA concentrations is 100-1000 times higher than that of 5-HT similar percentage changes imply that a very small part of the released 5-HT reaches the microdialysis probe under these conditions. When the 5-HT reuptake mechanism is blocked the extracellular 5-HT increases whereas extracellular 5-HIAA decreases mainly because of the 5-HT(1B) receptor-induced decrease in 5-HT release but in part also because of the inhibition of reuptake of 5-HT, both resulting in decreased formation of 5-HIAA. CONCLUSIONS Drug-induced changes in extracellular 5-HIAA levels can give valuable information on the effects of these drugs on the 5-HT release.

UI	MeSH Term	Description	Entries
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006897	Hydroxyindoleacetic Acid		5-HIAA,5-Hydroxy-3-Indoleacetic Acid,5-Hydroxyindolamine Acetic Acid,5 Hydroxy 3 Indoleacetic Acid,5 Hydroxyindolamine Acetic Acid,Acetic Acid, 5-Hydroxyindolamine,Acid, 5-Hydroxy-3-Indoleacetic,Acid, 5-Hydroxyindolamine Acetic,Acid, Hydroxyindoleacetic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012701	Serotonin	A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.	5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D012702	Serotonin Antagonists	Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.	5-HT Antagonist,5-HT Antagonists,5-Hydroxytryptamine Antagonist,5-Hydroxytryptamine Antagonists,Antiserotonergic Agent,Antiserotonergic Agents,Serotonin Antagonist,Serotonin Blockader,Serotonin Blockaders,Serotonin Receptor Antagonist,Serotonin Receptor Blocker,Antagonists, 5-HT,Antagonists, 5-Hydroxytryptamine,Antagonists, Serotonin,Serotonin Receptor Antagonists,Serotonin Receptor Blockers,5 HT Antagonist,5 HT Antagonists,5 Hydroxytryptamine Antagonist,5 Hydroxytryptamine Antagonists,Agent, Antiserotonergic,Agents, Antiserotonergic,Antagonist, 5-HT,Antagonist, 5-Hydroxytryptamine,Antagonist, Serotonin,Antagonist, Serotonin Receptor,Antagonists, 5 HT,Antagonists, 5 Hydroxytryptamine,Antagonists, Serotonin Receptor,Blockader, Serotonin,Blockaders, Serotonin,Blocker, Serotonin Receptor,Blockers, Serotonin Receptor,Receptor Antagonist, Serotonin,Receptor Antagonists, Serotonin,Receptor Blocker, Serotonin,Receptor Blockers, Serotonin
D017366	Serotonin Receptor Agonists	Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.	5-HT Agonists,5-Hydroxytryptamine Agonists,Serotonin Agonists,5-HT Agonist,5-Hydroxytrytamine Agonist,Receptor Agonists, Serotonin,Serotonergic Agonist,Serotonergic Agonists,Serotonin Agonist,Serotonin Receptor Agonist,5 HT Agonist,5 HT Agonists,5 Hydroxytryptamine Agonists,5 Hydroxytrytamine Agonist,Agonist, 5-HT,Agonist, 5-Hydroxytrytamine,Agonist, Serotonergic,Agonist, Serotonin,Agonist, Serotonin Receptor,Agonists, 5-HT,Agonists, 5-Hydroxytryptamine,Agonists, Serotonergic,Agonists, Serotonin,Agonists, Serotonin Receptor,Receptor Agonist, Serotonin
D017551	Microdialysis	A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.
D045604	Extracellular Fluid	The fluid of the body that is outside of CELLS. It is the external environment for the cells.	Interstitial Fluid,Intercellular Fluid,Extracellular Fluids,Fluid, Extracellular,Fluid, Intercellular,Fluid, Interstitial,Fluids, Extracellular,Fluids, Intercellular,Fluids, Interstitial,Intercellular Fluids,Interstitial Fluids