The effect of antiparkinsonian drugs on oxidative stress induced pathological [3H]dopamine efflux after in vitro rotenone exposure in rat striatal slices.

An in vitro model of mitochondrial dysfunction with subsequent oxidative stress was elaborated and utilized to study the effect of drugs, currently used for the treatment of Parkinson's disease, on pathological H(2)O(2)-evoked [(3)H]dopamine efflux and the formation of toxic dopamine metabolites in rat striatal slices. 60 min rotenone (0.1-10 muM) pretreatment decreased dopamine content and [(3)H]dopamine uptake, as well as ATP level and energy charge of the slices.

Modulation of dopaminergic neurotransmission in rat striatum upon in vitro and in vivo diclofenac treatment.

Diclofenac (DCF) is a widely used non-steroidal anti-inflammatory drug, which also act as a mitochondrial toxin. As it is known that selective mitochondrial complex I inhibition combined with mild oxidative stress causes striatal dopaminergic dysfunction, we tested whether DCF also compromise dopaminergic function in the striatum. [3H]Dopamine ([3H]DA) release was measured from rat striatal slices after in vitro (2 h, 10-25 micromol/L) or in vivo (3 mg/kg i.

Chromatographic analysis of dopamine metabolism in a Parkinsonian model.

The present study examined the metabolism of released dopamine from rat striatum upon chronic rotenone exposure. The sample separation was carried out by two-dimensional, reversed-phase and ion pair reversed-phase chromatography using on-line solid phase extraction enrichment. Reduced dopamine content and decreased extracellular level of [(3)H] and endogenous dopamine evoked by electrical stimulation indicated the injury of dopaminergic pathway.

Glutamate stimulation of acetylcholine release from myenteric plexus is mediated by endogenous nitric oxide.

Glutamate was found to be an excitatory neurotransmitter in the enteric nervous system. Although several lines of evidence indicate a role of glutamate in the regulation of gut motility and secretion the physiological significance of glutamatergic transmission is not clear yet. We studied the effect of glutamate on [3H]acetylcholine release and nicotinamide adenine dinucleotide phosphate-diaphorase staining in longitudinal muscle strips with attached myenteric plexus of guinea pig ileum.

Increased sensitivity of striatal dopamine release to H2O2 upon chronic rotenone treatment.

It is believed that both mitochondrial dysfunction and oxidative stress play important roles in the pathogenesis of Parkinson's disease (PD). We studied the effect of chronic systemic exposure to the mitochondrial inhibitor rotenone on the uptake, content, and release of striatal neurotransmitters upon neuronal activity and oxidative stress, the latter simulated by H(2)O(2) perfusion. The dopamine content in the rat striatum is decreased simultaneously with the progressive loss of tyrosine hydroxylase (TH) immunoreactivity in response to chronic intravenous rotenone infusion.

Muscarinic modulation of nitrergic neurotransmission in guinea-pig gastric fundus.

Muscarinic receptor activation by (4-Hydroxy-2-butynyl)-1-trimethylammonium-m-chlorocarbanilate chloride (McN-A-343) was investigated both on NADPH-d staining and on electrically induced responses in guinea-pig gastric fundus. McN-A-343 (10 micromol L(-1)) significantly increased the optical density of NADPH-d positive neurones, while blockade of nitric oxide synthase with N(omega)-nitro-L-arginine (L-NA) decreased it, suggesting facilitation of nitric oxide (NO) production. Electrical field stimulation (EFS; 2 Hz, 0.

Non-synaptic release of [3H]noradrenaline in response to oxidative stress combined with mitochondrial dysfunction in rat hippocampal slices.

Brain ischemia is frequently associated with oxidative stress in the reperfusion period. It is known that noradrenaline (NA) is released in excess under energy deprivation by the sodium-dependent reversal of the monoamine carrier. However, it is not known how oxidative stress affects NA release in the brain alone or in combination with energy deprivation.

Implication of ionotropic glutamate receptors in the release of noradrenaline in hippocampal CA1 and CA3 subregions under oxygen and glucose deprivation.

A strong linkage between adrenergic and glutamatergic systems exists in the CNS but it is still unclear whether the excessive release of noradrenaline under ischemic conditions is modulated by excitatory amino acids. We studied the effect of selective glutamate receptor antagonists on the release of [3H]noradrenaline evoked by glucose and oxygen deprivation in hippocampal CA1, CA3 and dentate gyrus subregions. The release of glutamate, aspartate and GABA was measured by HPLC.

Participation of endogenous nitric oxide in the effect of hypoxia in vitro on neuro-effector transmission in guinea-pig ileum.

The implication of endogenous nitric oxide in the effect of hypoxia on the neurotransmission in the enteric nervous system of guinea-pig ileum was studied in vitro. Three methodological approaches have been used: (i) Stretch-induced phases of peristaltic reflex in ileal segments; (ii) twitch contractions of longitudinal segments, evoked by electrical field stimulation; and (iii) release of [3H]acetylcholine from longitudinal muscle-myenteric plexus preparations, measured by liquid spectrophotometry. The effect of nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 100 microM) was studied under normoxic conditions.

Excessive release of [3H]noradrenaline and glutamate in response to simulation of ischemic conditions in rat spinal cord slice preparation: effect of NMDA and AMPA receptor antagonists.

In the present study we investigated the effects of NMDA and non-NMDA glutamate receptor antagonists on the ischemia-evoked release of [3H]noradrenaline from rat spinal cord slices. An in vitro ischemia model (oxygen and glucose deprivation) was used to simulate the ischemic conditions known to cause neuronal injury. Spinal cord slices were loaded with [3H]noradrenaline and superfused with Krebs solution in a micro-organ bath.

Involvement of nitric oxide in extrinsic nervous control of ileal contractile activity.

The experiments were carried out on guinea pig mesenteric nerve-ileal preparations (ileal segments with mesenteric nerves originating from the superior mesenteric ganglion) isolated at various distances from the ileocecal junction (ICJ). Contractile activity was recorded in the presence of hexamethonium (50 microM). On the background of electrical field stimulation (EFS; 0.

Role of different bombesin receptor subtypes mediating contractile activity in cat upper gastrointestinal tract.

Mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) are known to increase the motility of different segments in the gut. The present study was carried out to identify the bombesin receptor subtypes mediating the contractions induced by exogenous bombesin-like peptides in muscle strips isolated from cat esophagus, fundus, and duodenum. Both GRP-10 and NMB evoked concentration-dependent contractions in circular strips of esophagus and fundus and in longitudinal strips of the duodenum.

Non-adrenergic non-cholinergic neuron stimulation in the cat lower esophageal sphincter.

Both electrical field stimulation and nicotine produced non-adrenergic non-cholinergic (NANC) relaxation of the circular muscle strips from the cat lower esophageal sphincter in the presence of 5 microM guanethidine and 5 microM scopolamine. Low-frequency stimulation (2 Hz, 0.2 ms duration, supramaximal current intensity, 20-s train) provoked a transient relaxation, while at high-frequency stimulation (20 Hz) a slow restoration to the resting tone was observed.

Effect of hypoxia and glucose deprivation on ATP level, adenylate energy charge and [Ca2+]o-dependent and independent release of [3H]dopamine in rat striatal slices.

Release of [3H]dopamine ([3H]DA) from rat striatal slices kept under hypoxic or/and glucose-free conditions was measured using a microvolume perfusion method. The corresponding changes in nucleotide content were determined by reverse-phase high-performance liquid chromatography (RPHPLC). The resting release of [3H]DA was not affected by hypoxia, but under glucose-free conditions massive [Ca2+]o-independent release of [3H]DA was observed.

Excitatory and inhibitory effects of A1 and A2A adenosine receptor activation on the electrically evoked [3H]acetylcholine release from different areas of the rat hippocampus.

The modulation by adenosine analogues and endogenous adenosine of the electrically evoked release of [3H]acetylcholine ([3H]ACh) was compared in subslices of the three areas of the rat hippocampus (CA1, CA3, and dentate gyrus). The mixed A1/A2 agonist 2-chloroadenosine (CADO; 2-10 microM) inhibited, in a concentration-dependent manner, the release of [3H]ACh from the three hippocampal areas, being more potent in the CA1 and CA3 areas than in the dentate gyrus. The inhibitory effect of CADO (5 microM) on [3H]ACh release was prevented by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 50 nM) in the three hippocampal areas and was converted in an excitatory effect in the CA3 and dentate gyrus areas.

Differential changes in presynaptic modulation of transmitter release during aging.

The purpose of this study was to assess the functional role of presynaptic alpha 2-autoreceptors in noradrenergic transmission in the hippocampus and dopamine-2 heteroreceptors in cholinergic transmission in the striatum in young, adult, and senescent rats. Male and female Wistar rats (4, 12, and 24 months old) were used and the release of radioactivity from striatal and hippocampal slices that had been loaded either with [3H]choline or with [3H]norepinephrine was measured at rest and in response to field stimulation (2 Hz, 360 shocks). The release was challenged by sulpiride, a selective dopamine-2 receptor antagonist, and CH-38083, a selective alpha 2-adrenoceptor antagonist.

Release of acetylcholine and noradrenaline from the cholinergic and adrenergic afferents in rat hippocampal CA1, CA3 and dentate gyrus regions.

An attempt was made to study the release of acetylcholine (ACh) and noradrenaline and their presynaptic modulation in isolated slice preparations dissected from different subfields of the hippocampus: CA1, CA3 and the dentate gyrus. The slices were perfused and loaded with [3H]choline or with [3H]noradrenaline. The release in response to field stimulation was determined radiochemically and the content of transmitters was assayed by a chemiluminescent method or by HPLC combined with electrochemical detection.

GRP-preferring bombesin receptor subtype mediates contractile activity in cat terminal ileum.

Mammalian bombesin-like peptides, such as gastrin-releasing peptide and neuromedin B, are known to increase motility of different segments in the gut. The present study was carried out to identify the receptor subtype mediating these contractions of ileal longitudinal muscles in cats, in vitro. Both gastrin-releasing peptide (GRP) and neuromedin B (NMB) evoked concentration-dependent contractions of the strips.

Regulatory interactions among axon terminals affecting the release of different transmitters from rat striatal slices under hypoxic and hypoglycemic conditions.

An in vitro model of ischemia was utilized to study the effects of both oxygen and glucose depletion on transmitter release from rat striatal slices. The spontaneous and stimulation-evoked releases of tritiated dopamine, gamma-aminobutyric acid, glutamate, and acetylcholine were measured. Hypoxia increased the evoked release of glutamate and dopamine without effect on the resting release.

Effect of MK-801 on dopamine release evoked by hypoxia combined with hypoglycemia.

[3H]dopamine ([3H]DA) release was measured from rat striatal slices under normoxic and hypoxic conditions. In some experiments hypoxia was combined with glucose withdrawal. Hypoxia increased the evoked release of dopamine without affecting resting release.

The dual effect of BAY K 8644 on excitation-contraction coupling in gastric smooth muscle.

1. BAY K 8644 at concentrations of 10(-10)-10(-6) M had a stimulant effect on the spontaneous electrical and contractile activity of smooth muscle preparations from cat and guinea pig stomach. 2.

Inhibitory effect of hypoxic condition on acetylcholine release is partly due to the effect of adenosine released from the tissue.

Isolated longitudinal muscle strip with Auerbach's plexus attached was used to study the stimulation-evoked release of 3H-acetylcholine (3H-ACh) under normoxic and hypoxic conditions. Hypoxia reduced the release of ACh. Theophylline, a purinoceptor P1 antagonist and vinpocetine, an antiischemic compound partly reversed the effect of hypoxia.

Bombesin-induced changes in membrane potential-dependent phasic contractions of cat gastric muscle.

Electrical and contractile activities of smooth muscle strips isolated from the circular muscle layer of cat gastric antrum were studied using the sucrose gap technique. Bombesin (10(-8) mol/l) depolarized the gastric muscle; this was accompanied by an increase in the strip tone, in the plateau action potential frequency and in both the frequency and the amplitude of the spike potentials as well as by a shortening of the plateau action potential duration. Both the frequency and the amplitude of the phasic contractions increased thereafter.