Kinetic and pharmacological properties of [3H]-histamine transport into cultured type 1 astrocytes from neonatal rats |
| |
Authors: | D Osredkar T Burnik-Papler B Pe?avar V Kralj-Igli? M Kr?an |
| |
Institution: | (1) Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Si-1000 Ljubljana, Slovenia;(2) Laboratory of Clinical Biophysics, Faculty of Medicine, University of Ljubljana, Si-1000 Ljubljana, Slovenia |
| |
Abstract: | Objective and design: Astrocytes actively participate in the inactivation of neurotransmitters. In this work we elucidated the contribution of astrocytes
in clearance of histamine, a process which has not yet been fully clarified.
Methods: The characteristics of 3H]-histamine uptake were determined in cultured neonatal rat type 1 astrocytes and histamine-N-methyl-transferase expression
was determined using RT-PCR.
Results: These cells transport 3H]-histamine in a time- and concentration-dependent manner. The histamine clearance by astrocytes was described by a mathematical
model including two processes: electrodiffusion and active transport. A further analysis of kinetic parameters of a carrier-operated
transport revealed a single transport system with Michaelis constant (Km) of 3.5 ± 0.8 μM and a maximal uptake rate (Vmax) of 7.9 ± 0.3 pmol/mg protein/min. From drugs tested amitriptyline, desipramine, mepyramine and cimetidine significantly
decreased 3H]-histamine uptake. Taken-up histamine could be metabolically degraded in cultured astrocytes, since they express mRNA for
enzyme histamine-N-methyltransferase.
Conclusions: Astrocytes participate in the clearance of extracellular histamine by electrodiffusion and active transport by a yet not identified
carrier. Taken up histamine can be converted to tele-methylhistamine within astrocytes thus indicating the involvement of
astrocytes not only in clearance but also in the inactivation of histamine.
Received 24 November 2007; returned for revision 4 January 2008; received from final revision 22 May 2008; accepted by A.
Falus 3 November 2008 |
| |
Keywords: | :" target="_blank">: Histamine Histamine uptake Histamine electrodiffusion Astrocyte Rat |
本文献已被 SpringerLink 等数据库收录! |
|