Search results for "agonists"
showing 10 items of 1616 documents
Heterocyclisch anellierte Steroide aus 2-Hydroxymethylen-canrenon
1995
A-ring annulated heterocycles, the isoxazole 6, the pyrazoles 8 and the pyrimidines 9 are prepared starting from 2-hydroxymethylene canrenone 1. Binding studies were carried out with the compounds 1 and 6-8 using estrogen, progesterone, androgen, gluco- and mineralocorticoid receptors as well as the serum proteins SHBG and CBG: the substances were inactive on the receptor level. 1, 7 and 8a show weak binding affinity to CBG.
Association between use of novel glucose-lowering drugs and COVID-19 hospitalization and death in patients with type 2 diabetes: a nationwide registr…
2022
Abstract Aims Type 2 diabetes (T2DM) in patients with coronavirus disease-19 (COVID-19) is associated with a worse prognosis. We separately investigated the associations between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of COVID-19 hospitalization and death. Methods and results Patients with T2DM registered in the Swedish National Patient Registry and alive on 1 February 2020 were included. ‘Incident severe COVID-19’ was defined as the first hospitalization and/or death from COVID-19. A modified Poisson regression approach was applied to a 1:1 propensity sc…
Transient oligemia is associated with long-term changes in binding densities of cortical inhibitory GABAA receptors in the rat brain
2009
Recently, we could demonstrate in rats that a short transient oligemic period of only 20-minute duration, induced by systemic hypotension, resulted in a transient decline of spatial memory capacities without any histological damage over a subsequent period of 6 months. In our present study, we checked for more subtle alterations within the highly vulnerable hippocampal CA1 subfield using quantification of neuronal cell density and semi-quantitative analysis of the ischemia-sensitive protein MAP2. Since hippocampal excitatory and inhibitory neurotransmitter receptors are crucially involved in spatial memory processes, quantitative in vitro receptor autoradiography was performed using [(3)H]M…
Stimulatory and inhibitory effects of ethanol on hippocampal acetylcholine release
1998
Using the microdialysis technique and sensitive HPLC procedures for the determination of acetylcholine (ACh) and ethanol, we investigated the release of ACh in rat hippocampus after acute ethanol administration. Systemic administration of ethanol (0.8 and 2.4 g/kg i.p.) led to peak ethanol concentrations of 21 and 42 mM in the hippocampus, respectively. The high dose caused a long-lasting inhibition of basal ACh release by up to 33%. Local infusion of scopolamine (1 microM) enhanced hippocampal ACh release up to eightfold in the presence of neostigmine (10 microM), and this stimulated release was also inhibited after systemic ethanol administration (by up to 45%). The low dose of ethanol (0…
Dietary exposure in utero and during lactation to a mixture of genistein and an anti-androgen fungicide in a rat mammary carcinogenesis model
2015
Endocrine disruptors may play substantial roles in the high incidence of breast cancer. We previously described how early exposure to the mixture of phytoestrogen genistein (G) and the anti-androgen vinclozolin (V) affects peripubertal mammary development. This study evaluates the carcinogenic potential of exposure to V alone or associated with G from conception until weaning in Wistar rats. Dams were exposed to V, G or GV during pregnancy/lactation. At PND50 offspring were treated with DMBA[7,12-dimethylbenz(a)anthracene]. V or GV maternal exposure decreased number of DMBA-induced mammary tumors in the offspring, without significant modifications in tumor incidence, multiplicity and latenc…
Histamine and spontaneously released mast cell granules affect the cell growth of human hepatocellular carcinoma cells
2007
The role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H(1) and …
Structural Mechanism of N-Methyl-D-Aspartate Receptor Type 1 Partial Agonism
2012
N-methyl-D-aspartate (NMDA) receptors belong to a family of ionotropic glutamate receptors that contribute to the signal transmission in the central nervous system. NMDA receptors are heterotetramers that usually consist of two GluN1 and GluN2 monomers. The extracellular ligand-binding domain (LBD) of a monomer is comprised of discontinuous segments that form the functional domains D1 and D2. While the binding of a full agonist glycine to LBD of GluN1 is linked to cleft closure and subsequent ion-channel opening, partial agonists are known to activate the receptor only sub-maximally. Although the crystal structures of the LBD of related GluA2 receptor explain the mechanism for the partial a…
Enhanced tonic GABAA inhibition in typical absence epilepsy
2009
The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired γ-aminobutyric acid (GABA)-ergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent 'tonic' inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT-1 in the genetic models tested, and GAT-1 is crucial in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best character…
Extended-release guanfacine hydrochloride in 6-17-year olds with ADHD: a randomised-withdrawal maintenance of efficacy study.
2015
Background Extended-release guanfacine hydrochloride (GXR), a selective α2A-adrenergic agonist, is a nonstimulant medication for attention-deficit/hyperactivity disorder (ADHD). This phase 3, double-blind, placebo-controlled, randomised-withdrawal study evaluated the long-term maintenance of GXR efficacy in children/adolescents with ADHD. Methods Children/adolescents (6–17 years) with ADHD received open-label GXR (1–7 mg/day). After 13 weeks, responders were randomised to GXR or placebo in the 26-week, double-blind, randomised-withdrawal phase (RWP). The primary endpoint was the percentage of treatment failure (≥50% increase in ADHD Rating Scale version IV total score and ≥2-point increase …
GABAC receptors are functionally expressed in the intermediate zone and regulate radial migration in the embryonic mouse neocortex
2010
Radial neuronal migration in the cerebral cortex depends on trophic factors and the activation of different voltage- and ligand-gated channels. To examine the func- tional role of GABAC receptors in radial migration we ana- lyzed the effects of specific GABAA and GABAC receptor antagonists on the migration of BrdU-labeled neurons in vitro using organotypic neocortical slice cultures. These experi- ments revealed that the GABAA specific inhibitor bicuculline methiodide facilitated neuronal migration, while the GABAC specific inhibitor (1,2,5,6-tetrahydropyridine-4-yl) methylphos- phinic-acid (TPMPA) impeded migration. Co-application of TPMPA and bicuculline methiodide or the unspecific ionot…