Search results for "Receptor"

New approaches in the treatment of Adamantiades-Behçet's disease.

2005

Purpose of review To update clinicians on the recent advances in the treatment of Adamantiades-Behcet's disease. Recent findings Interferon-α-2a and infliximab have proved able to induce prompt remission in the vast majority of Adamantiades-Behcet's patients with DMARD-resistant uveoretinitis. Efficacy of interferon-α-2a has also been reported for mucocutaneous lesions, arthritis, and (more anecdotally) for neuro-Behcet, while results from small case series suggest that infliximab is beneficial for mucocutaneous lesions and (more anecdotally) for arthritis and gastro-intestinal manifestations. Two cases of neuro-Behcet treated with infliximab showed a complete resolution. Finally, in a rand…

Control of Acetylcholine Release and of Intestinal Motility by Subtypes of Muscarine Receptors

1988

Two types of neuronal muscarine receptors have been investigated in the myenteric plexus preparation of the guinea-pig small intestine: 1. Presynaptic receptors activation of which inhibits the depolarization-evoked release of acetylcholine. Pirenzepine and dicyclomine have low affinities to the release-inhibitory receptors (pA2 values 6.9 and 7.6) which suggests that the presynaptic receptors (similar to the smooth muscle receptors) belong to the M2 subtype. The inhibition of the electrically-evoked acetylcholine release by muscarine (0.01 - 1 μmol/1) was not affected by forskolin (1μmol/l). This indicates that cyclic AMP is not crucially involved in the muscarinic inhibition of acetylchol…

The role of vagus activity in the presynaptic control of noradrenaline release from rabbit atria.

1990

Abstract On various heart preparations with the autonomic innervation left intact, vagus nerve stimulation (VNS) has been found to reduce the amount of noradrenaline (NA) that is released in response to sympathetic nerve stimulation (SNS). The following experiments were carried out on an innervated rabbit perfused atria preparation in which the overflow of NA and acetylcholine (ACh) could be determined simultaneously. VNS impulses applied at a fixed time interval before the corresponding SNS impulses reduced NA overflow when the interval was 3–10 ms (early peak) or 200–283 ms (late peak of inhibition). VNS applied 30–167 ms before SNS had no significant effect (“ineffectual period”). Both i…

Neurodegenerative changes are prevented by Erythropoietin in the pmn model of motoneuron degeneration

2014

Motoneuron diseases are fatal neurodegenerative disorders characterized by a progressive loss of motoneurons, muscle weakness and premature death. The progressive motor neuronopathy (pmn) mutant mouse has been considered a good model for the autosomal recessive childhood form of spinal muscular atrophy (SMA). Here, we investigated the therapeutic potential of Erythropoietin (Epo) on this mutant mouse. Symptomatic or pre-symptomatic treatment with Epo significantly prolongs lifespan by 84.6% or 87.2% respectively. Epo preserves muscle strength and significantly attenuates behavioural motor deficits of mutant pmn mice. Histological and metabolic changes in the spinal cord evaluated by immunoh…

The pathological hallmarks of Alzheimer’s disease derive from compensatory responses to NMDA receptor insufficiency

2018

AbstractAlzheimer’s disease is characterized by intracellular aggregates of hyperphosphorylated tau protein and extracellular plaques of amyloid β peptide, a product of APP processing. The origin of these pathological hallmarks has remained elusive. Here, we have tested the idea that both alterations, at the onset of the disease, may constitute compensatory responses to the same causative and initial trigger, namely NMDA receptor insufficiency. Treatment of rat cortical neurons with the specific NMDA receptor antagonist AP5 within 4 h caused a significant increase in tau phosphorylation at the AT8 and S404 epitopes as well as an increase in APP expression and Aβ 40 secretion. Single intrape…

2015

Several point mutations have been identified in human aquaporins, but their effects on the function of the respective aquaporins are mostly enigmatic. We analyzed the impact of the aquaporin 2 mutation V71M, which causes nephrogenic diabetes insipidus in humans, on aquaporin structure and activity, using the bacterial aquaglyceroporin GlpF as a model. Importantly, the sequence and structure around the V71M mutation is highly conserved between aquaporin 2 and GlpF. The V71M mutation neither impairs substrate flux nor oligomerization of the aquaglyceroporin. Therefore, the human aquaporin 2 mutant V71M is most likely active, but cellular trafficking is probably impaired.

Mechanisms of C-reactive protein-induced blood-brain barrier disruption.

2009

Background and Purpose— Increased mortality after stroke is associated with brain edema formation and high plasma levels of the acute phase reactant C-reactive protein (CRP). The aim of this study was to examine whether CRP directly affects blood–brain barrier stability and to analyze the underlying signaling pathways. Methods— We used a cell coculture model of the blood–brain barrier and the guinea pig isolated whole brain preparation. Results— We could show that CRP at clinically relevant concentrations (10 to 20 μg/mL) causes a disruption of the blood–brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fcγ receptors CD16/32 fo…

Cl−uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1

2004

GABA is the principal inhibitory neurotransmitter in the mature brain, but during early postnatal development the elevated [Cl−]i in immature neocortical neurones causes GABAA receptor activation to be depolarizing. The molecular mechanisms underlying this intracellular Cl− accumulation remain controversial. Therefore, the GABA reversal potential (EGABA) or [Cl−]i in early postnatal rat neocortical neurones was measured by the gramicidin-perforated patch-clamp method, and the relative expression levels of the cation−Cl− cotransporter mRNAs (in the same cells) were examined by semiquantitative single-cell multiplex RT-PCR to look for statistical correlations with [Cl−]i. The mRNA expression …

Induction of neurosteroid synthesis by NMDA receptors in isolated rat retina: a potential early event in excitotoxicity

1998

Here we investigated the possible regulation of neurosteroidogenesis by N-methyl-D-aspartic acid (NMDA) receptor activation and addressed the hypothesis that neurosteroid synthesis may be involved in acute excitotoxicity. In the isolated retina, exposure to NMDA modified pregnenolone and pregnenolone sulphate formation. This effect was dose and time dependent, the synthesis being increased by relatively moderate NMDA doses (1-100 microM) within 30 min exposure and reduced to its control value by 60 min or by raising drug concentrations. NMDA-stimulated neurosteroid synthesis was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) and 3(2-ca…

Pregnenolone sulfate modulates NMDA receptors, inducing and potentiating acute excitotoxicity in isolated retina

1998

Pregnenolone sulfate (PS) acts as a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptor-mediated responses. In the retina, we previously observed that the synthesis of pregnenolone and PS increases after stimulation of NMDA receptors and blockade of the synthesis reduces retinal cell death. This study was carried out to explore in the isolated and intact retina the possible role of PS in NMDA-induced excitotoxicity. Lactate dehydrogenase (LDH) measurements and morphological analysis revealed that a 90-min exogenous application of PS at 0.1-500 microM concentrations potentiated NMDA-induced cell death and at 50-500 microM concentrations caused cytotoxicity. After 45 min, ei…