Avtor/Urednik     Perdan-Pirkmajer, Katja; Mavri, Janez; Kržan, Mojca
Naslov     Histamine (re)uptake by astrocytes: an experimental and computational study
Tip     članek
Vir     J Mol Model
Vol. in št.     Letnik 16, št. 6
Leto izdaje     2010
Obseg     str. 1151-8
ISSN     1610-2940
Jezik     eng
Abstrakt     Astrocytes participate in the clearance of neurotransmitters by their uptake and subsequent enzymatic degradation. Histamine as a polar and/or protonated molecule must use a carrier to be transported across the cell membrane, although a specific histamine transporter has not been elucidated, yet. In this work we upgraded the kinetic studies of histamine uptake into neonatal rat cultured type 1 astrocytes with quantum chemical calculations of histamine pKa values in conjunction with Langevin dipoles solvation model as the first step toward microscopic simulation of transport. Our results indicate that astrocytes transport histamine by at least two carrier mediated processes, a concentration gradient dependent passive and a sodium-dependent and ATP-driven active transport. We also demonstrated that histamine protonation states depend on the polarity of the environment. In conclusion we suggest that histamine, a polar molecule at physiological pH uses at least two different mechanisms for its uptake into astrocytes -an electrodiffusion and Na(+)-dependent and ouabain sensitive active process. We emphasize relevance of knowledge of histamines protonation states at the rate limiting step of its transport for microscopic simulation that will be possible when structure of histamine transporter is known.
Deskriptorji     ASTROCYTES
HISTAMINE
KINETICS
BIOLOGICAL TRANSPORT
SODIUM
OUABAIN
CELLS, CULTURED
COMPUTER SIMULATION
RATS