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Kinetic and pharmacological properties of š(3)Hđ-histamine transport into cultured type 1 astrocytes from neonatal rats
Osredkar, David ...
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 š(3)Hđ-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 š(3)Hđ-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 (K(m)) of 3.5 +/- 0.8 muM and a maximal uptake rate (V(max)) of 7.9 +/- 0.3 pmol/mg protein/min. From drugs tested amitriptyline, desipramine, mepyramine and cimetidine significantly decreased š(3)Hđ-histamine uptake. Taken-up histamine could be metabolically degraded in cultured astrocytes, since they express mRNA for enzyme histamine-N-methyltransferase.Conclusion: 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 theinactivation of histamine.
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