Vpliv dopaminergičnih učinkovin na privzem histamina v astrocite novorojene podgane

Glavač, Kaja (avtor), Kržan, Mojca (mentor)

Histamin uvrščamo med biogene amine in ga najdemo v mnogih tkivih v telesu. V osrednjem živčnem sistemu ima vlogo živčnega prenašalca. Za vse nevrotransmiterje velja, da bi v presežnih koncentracijah lahko povzročali nevrotoksičnost. Zato se morajo po sprostitvi v sinaptično špranjo in delovanju na tarčni receptor odstraniti iz sinapse z izplavljanjem v zunajcelično tekočino, s ponovnim privzemom v celice, iz katerih so se sprostili ali s privzemom v celice glije, ki obdajajo sinapso. Astrociti, ki skupaj s presinaptično in postsinaptično živčno celico tvorijo tridelno sinapso, tako igrajo pomembno vlogo pri inaktivaciji in odstranjevanju histamina iz sinaptične špranje. Ker ima molekula histamina v fizioloških razmerah (pH 7,4) pozitiven naboj, potrebuje za prenos preko membrane prenašalca. Marsikaj je že znanega o privzemu histamina, a specifičnega prenašalca zanj še ne poznamo. Zato smo se odločili raziskati, kako se histamin privzema v astrocite, izolirane iz možganske skorje novorojene podgane. Najprej smo prišli do ugotovitve, da je privzem histamina v astrocite neonatalne podgane od koncentracije in pH medija odvisen proces. Pri manjši vrednosti pH sta se zmanjšali tako afiniteta kot kapaciteta privzema histamina v astrocite, je pa bil privzem še vedno večji v območju večjih koncentracij dodanega 3H- histamina. Ugotovili smo, da se histamin privzema v astrocite možganske skorje neonatalne podgane preko prenašalca z nizko afiniteto in visoko kapaciteto. Rezultati inhibicije privzema histamina v astrocite z decinijem 22, ki je inhibitor transporterja za organske katione, so pokazali, da se histamin zelo verjetno prenaša preko transporterja za organske katione. 100 mM koncentracija decinija 22 skoraj popolnoma inhibira privzem histamina v astrocite. Preverili smo tudi vpliv drugih monoaminov na privzem histamina v astrocite neonatalne podgane in ugotovili, da ima največji vpliv dopamin. Zato nas je zanimal še vpliv prekurzorjev dopamina in dopaminu podobnih snovi. Izkazalo se je, da snovi, ki vstopajo v dopaminergične nevrone – tirozin, 6-hidroksidopamin in selegilin – bolj zmanjšajo privzem histamina v astrocite novorojenih podgan kot učinkovine, ki delujejo na membrani – apomorfin in L-DOPA – ki na privzem praktično nista imela vpliva.

• Jezik: Slovenski jezik
• Ključne besede: histamin, astrociti, privzem histamina, OCT, dopamin
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2019
• PID: 20.500.12556/RUL-112845
• Datum objave v RUL: 15.11.2019

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: The influence of dopaminergic drugs on histamine uptake into neonatal rat astrocytes

Izvleček

Histamine is classified as a biogenic amine and is found in many tissues in the body. In the central nervous system, it plays the role of a nerve transporter. All neurotransmitters are thought to be neurotoxic at excess concentrations. So after release into synaptic cleft and interaction with receptor they should be removed from synapses by release into extracellular fluid, re-uptake into cells from which they have been released or uptake, into the glia cells surrounding the synapse. Astrocytes, which together with the presynaptic and postsynaptic nerve cells, form a three-part synapse, thus play an important role in the inactivation and removal of histamine from the synaptic cleft. Since the histamine molecule is positively charged under physiological conditions (pH 7.4), it needs to be transported by transporter through membrane. Although there is already a lot known about histamine uptake, the specific transporter remains unknown. Therefore, we decided to investigate histamine uptake in astrocytes isolated from the cerebral cortex of a newborn rat. We first came to the conclusion that the uptake of histamine into neonatal rat astrocytes is a concentration-dependent and ph-dependent process. At more acidic pH, both affinity and capacity for histamine uptake into astrocytes decreased, and uptake was still greater in the range of higher concentrations of 3H-histamine added. We came to a conclusion that histamine is transported in astrocytes from cerebral cortex of neonatal rat by low-affinity and high-capacity transporter system. The results of inhibition of histamine uptake into astrocytes by decinium 22, which is an inhibitor of the organic cation transporter, have shown that histamine is very likely to be transmitted via the organic cation transporter. Decinium 22 in concentration of 100 mM almost completely inhibited histamine uptake into astrocytes. We also examined the effect of other monoamines on histamine uptake into neonatal rat astrocytes and found that dopamine had the greatest influence. Therefore, we were also interested in the influence of dopamine precursors and dopamine-like substances. Substances entering dopaminergic neurons – tyrosine, 6-hydroxydopamine and selegiline – have been shown to reduce the uptake of histamine into neonatal rat astrocytes more than membrane-acting agents – apomorphine and L-DOPA – which had little effect on uptake.

• Ključne besede: histamine, astrocytes, histamine uptake, OCT, dopamine