Effect of subchronic exposure to ambient fine and ultrafine particles on rat motor activity and striatal dopaminergic transmission.

Alterations in dopaminergic transmission are associated with neurological disorders, such as depression, autism, and Parkinson's disease. Exposure of rats to ambient fine (FP) or ultrafine (UFP) particles induces oxidative and inflammatory responses in the striatum, a neuronal nucleus with dense dopaminergic innervation and critically involved in the control of motor activity. We used an system to evaluate the effect of inhalation exposure to FP and UFP on motor activity and dopaminergic transmission.

In vitro exposure to ambient fine and ultrafine particles alters dopamine uptake and release, and D receptor affinity and signaling.

The exposure to environmental pollutants, such as fine and ultrafine particles (FP and UFP), has been associated with increased risk for Parkinson's disease, depression and schizophrenia, disorders related to altered dopaminergic transmission. The striatum, a neuronal nucleus with extensive dopaminergic afferents, is a target site for particle toxicity, which results in oxidative stress, inflammation, astrocyte activation and modifications in dopamine content and D receptor (DR) density. In this study we assessed the in vitro effect of the exposure to FP and UFP on dopaminergic transmission, by evaluating [H]-dopamine uptake and release by rat striatal isolated nerve terminals (synaptosomes), as well as modifications in the affinity and signaling of native and cloned DRs.

Histamine H receptor activation reduces the impairment in prepulse inhibition (PPI) of the acoustic startle response and Akt phosphorylation induced by MK-801 (dizocilpine), antagonist at N-Methyl-d-Aspartate (NMDA) receptors.

We have investigated the effect of the local activation of histamine H receptors (HRs) in the rat prefrontal cortex (PFCx) on the impairment of pre-pulse inhibition (PPI) of the startle response induced by the systemic administration of MK-801, antagonist at glutamate N-Methyl-d-Aspartate (NMDA) receptors, and the possible functional interaction between HRs and MK-801 on PFCx dopaminergic transmission. Infusion of the HR agonist RAMH (19.8 ng/1 μl) into the PFCx reduced or prevented the inhibition by MK-801 (0.

Adenosine A and histamine H receptors interact at the cAMP/PKA pathway to modulate depolarization-evoked [H]-GABA release from rat striato-pallidal terminals.

We previously reported that the activation of histamine H receptors (HRs) selectively counteracts the facilitatory action of adenosine A receptors (ARs) on GABA release from rat globus pallidus (GP) isolated nerve terminals (synaptosomes). In this work, we examined the mechanisms likely to underlie this functional interaction. Three possibilities were explored: (a) changes in receptor affinity for agonists induced by physical AR/HR interaction, (b) opposite actions of ARs and HRs on depolarization-induced Ca entry, and (c) an AR/HR interaction at the level of adenosine 3',5'-cyclic monophosphate (cAMP) formation.

Differential expression and signaling of the human histamine H receptor isoforms of 445 and 365 amino acids expressed in human neuroblastoma SH-SY5Y cells.

In stably-transfected human neuroblastoma SH-SY5Y cells, we have compared the effect of activating two isoforms of 445 and 365 amino acids of the human histamine H receptor (hHR and hHR) on [S]-GTPγS binding, forskolin-induced cAMP formation, depolarization-induced increase in the intracellular concentration of Ca ions ([Ca]i) and depolarization-evoked [H]-dopamine release. Maximal specific binding (B) of [H]-N-methyl-histamine to cell membranes was 953 ± 204 and 555 ± 140 fmol/mg protein for SH-SY5Y-hHR and SH-SY5Y-hHR cells, respectively, with similar dissociation constants (K, 0.86 nM and 0.

Differential homologous desensitization of the human histamine H receptors of 445 and 365 amino acids expressed in CHO-K1 cells.

Histamine H receptors (HRs) signal through Gα proteins and are found in neuronal cells as auto- and hetero-receptors. Alternative splicing of the human HR (hHR) originates 20 isoforms, and the mRNAs of two receptors of 445 and 365 amino acids (hHR and hHR) are widely expressed in the human brain. We previously showed that the hHR stably expressed in CHO-K1 cells experiences homologous desensitization.

The naturally occurring mutation Y197C does not affect the expression or signaling of the human histamine H receptor.

There is evidence for genetic polymorphism within the human histamine H receptor (hHR), and a Tyr to Cys exchange at position 197 (Y197C), located in the amino terminus of the fifth transmembrane domain, has been reported. In this work we compared the expression and the pharmacological and signaling properties of wild-type (hHR) and mutant (hHR) receptors transiently expressed in CHO-K1 cells. The hHR cDNA was created by overlap extension PCR amplification.

Heterologous, PKC-Mediated Desensitization of Human Histamine H3 Receptors Expressed in CHO-K1 Cells.

Desensitization is a major mechanism to regulate the functional response of G protein-coupled receptors. In this work we studied whether the human histamine H3 receptor of 445 amino acids (hH3R445) experiences heterologous desensitization mediated by PKC activation. Bioinformatic analysis indicated the presence of Serine and Threonine residues susceptible of PKC-mediated phosphorylation on the third intracellular loop and the carboxyl terminus of the hH3R445.

Histamine H3 receptor activation inhibits dopamine synthesis but not release or uptake in rat nucleus accumbens.

We studied the effect of activating histamine H3 receptors (H3Rs) on rat nucleus accumbens (rNAcc) dopaminergic transmission by analyzing [(3)H]-dopamine uptake by synaptosomes, and dopamine synthesis and depolarization-evoked [(3)H]-dopamine release in slices. The uptake of [(3)H]-dopamine by rNAcc synaptosomes was not affected by the H3R agonist RAMH (10(-10)-10(-6) M). In rNAcc slices perfusion with RAMH (1 μM) had no significant effect on [(3)H]-dopamine release evoked by depolarization with 30 mM K(+) (91.

Histamine H3 receptor activation counteracts adenosine A2A receptor-mediated enhancement of depolarization-evoked [3H]-GABA release from rat globus pallidus synaptosomes.

High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus (GP), a neuronal nucleus in the basal ganglia involved in the control of motor behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied whether H3R activation modified the previously reported enhancing action of adenosine A2A receptor (A2AR) stimulation on depolarization-evoked [(3)H]-GABA release. At 3 and 10 nM, the A2AR agonist CGS-21680 enhanced [(3)H]-GABA release induced by high K(+) (20 mM) and the effect of 3 nM CGS-21680 was prevented by the A2AR antagonist ZM-241385 (100 nM).

Homologous desensitization of human histamine H₃ receptors expressed in CHO-K1 cells.

Histamine H₃ receptors (H₃Rs) modulate the function of the nervous system at the pre- and post-synaptic levels. In this work we aimed to determine whether, as other G protein-coupled receptors (GPCRs), H₃Rs desensitize in response to agonist exposure. By using CHO-K1 cells stably transfected with the human H₃R (hH3R) we show that functional responses (inhibition of forskolin-induced cAMP accumulation in intact cells and stimulation of [(35)S]-GTPγS binding to cell membranes) were markedly reduced after agonist exposure.

Histamine H₃ receptors modulate depolarization-evoked [³H]-noradrenaline release from rat olfactory bulb slices.

We have studied the effect of histamine H(3) receptor (H(3)R) activation on the depolarization-evoked release of labeled neurotransmitters from slices of the rat olfactory bulb (rOB). The presence of pre-synaptic H(3)Rs was evidenced by the specific binding of the H(3)R ligand N-α-[methyl-(3)H]histamine to membranes from rOB synaptosomes (maximum binding, B(max), 106 ± 19 fmol/mg protein; dissociation constant, K(d), 0.68 ± 0.