Kinetic and pharmacological properties of [(3)H]-histamine transport into cultured type 1 astrocytes from neonatal rats.
OBJECTIVE
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 [(3)H]-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 [(3)H]-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 microM 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 [(3)H]-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.
Osredkar
D
D
Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Burnik-Papler
T
T
Pecavar
B
B
Kralj-Iglic
V
V
Krzan
M
M
D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006632:Histamine / Q000737:chemistry / Q000378:metabolism*; D006633:Histamine Antagonists / Q000378:metabolism; D006637:Histamine N-Methyltransferase / Q000378:metabolism; D008962:Models, Theoretical; D051381:Rats; D011968:Receptors, Histamine / Q000378:metabolism; D014316:Tritium / Q000737:chemistry / Q000378:metabolism*
D000928:Antidepressive Agents; D006633:Histamine Antagonists; D011968:Receptors, Histamine; D014316:Tritium; D006632:Histamine; D006637:Histamine N-Methyltransferase