Search results for "cyclic"
showing 10 items of 2439 documents
Pharmacological Characterization of Loss of Function Mutations of the Human Melanocortin 1 Receptor That Are Associated with Red Hair
2004
Variation in skin color is the major host risk factor for melanoma and other forms of skin cancer. Individuals with red hair show an increased ratio of phaeomelanin to eumelanin in both hair and skin. This ratio is regulated by the melanocortin (MC) 1 receptor. There are several common point mutations in the human MC1 receptor that are overrepresented in North European red-heads, and in individuals with pale skin. In order to determine the functional significance of these mutations, we expressed the Asp84Glu, Val92Met, Arg163Gln, and Asp294His variants of the human MC1 receptors in eukaryotic cells and determined their ability to bind alpha-melanocyte stimulating hormone (MSH) peptides and …
Stabilization of Perivascular Mast Cells by Endothelial CNP (C-Type Natriuretic Peptide)
2020
Objective: Activated perivascular mast cells (MCs) participate in different cardiovascular diseases. Many factors provoking MC degranulation have been described, while physiological counterregulators are barely known. Endothelial CNP (C-type natriuretic peptide) participates in the maintenance of vascular barrier integrity, but the target cells and mechanisms are unclear. Here, we studied whether MCs are regulated by CNP. Approach and Results: In cultured human and murine MCs, CNP activated its specific GC (guanylyl cyclase)-B receptor and cyclic GMP signaling. This enhanced cyclic GMP–dependent phosphorylation of the cytoskeleton-associated VASP (vasodilator-stimulated phosphoprotein) and…
TREATMENT WITH SILDENAFIL PREVENTS IMPAIRMENT OF LEARNING IN RATS BORN TO PRE-ECLAMPTIC MOTHERS
2010
Pre-eclampsia is an important hypertensive pregnancy disorder and a main cause of maternal and fetal morbidity and mortality Children born from mothers with preeclampsia may present cognitive deficits The mechanisms leading to this cognitive impairment remain unclear and no treatments to improve it have been tested Pre-eclampsia is associated with impaired regulation of the nitric oxide 3 5 guanosine monophosphate cyclic (cGMP) pathway, which modulates some cognitive functions We hypothesized that alterations in the NO-cGMP pathway would be involved in the mechanisms leading to cognitive impairment in rats born to pre-eclamptic mothers and that treatment with sildenafil an inhibitor of the …
NADPH Oxidase Accounts for Enhanced Superoxide Production and Impaired Endothelium-Dependent Smooth Muscle Relaxation in BKβ1 −/− Mice
2006
Objective— Nitric oxide (NO)-induced vasorelaxation involves activation of large conductance Ca 2+ -activated K + channels (BK). A regulatory BKβ1 subunit confers Ca 2+ , voltage, and NO/cGMP sensitivity to the BK channel. We investigated whether endothelial function and NO/cGMP signaling is affected by a deletion of the β1-subunit. Methods and Results— Vascular superoxide in BKβ1 −/− was measured using the fluorescent dye hydroethidine and lucigenin-enhanced chemiluminescence. Vascular NO formation was analyzed using electron paramagnetic resonance (EPR), expression of NADPH oxidase subunits, the endothelial NO synthase (eNOS), the soluble guanylyl cyclase (sGC), as well as the activity a…
Histamine-sensitive adenylate cyclase of human gastric mucosa: a model for H2-receptor excitation.
1978
Recent studies revealed that human gastric mucosa contains a histamine-sensitive adenylate cyclase which is almost completely localized within the acid-secreting area of the stomach. In an attempt to further characterize the effector system of histamine’s action, we compared the effects of H 1 — and H 2-receptor agonists upon the adenylate cyclase in human fundic gastric mucosa.
Calcium Dependence of the Mechanical Response Evoked by Okadaic Acid in Smooth Muscle
1995
The effects of okadaic acid (OA), obtained from a culture of the marine dinoflagellate Prorocentrum Lima were studied on isolated strips of rat myometrium. The contractile response evoked by OA at 5, 10, and 20 μM in normal physiological solution was unaffected in the presence of tetrodotoxin (10 μM), indomethacin (3 μM), or a cocktail of antagonists which blocked muscarinic, adrenergic, histaminergic, serotonergic, and opioid receptors. Similarly, the response to OA was unaffected in the presence of nifedipine at a concentration (1 μM) which completely or highly blocked the response to KCl (60 mM), oxytocin (1 μM), or acetylcholine (100 μM). In a Ca 2+ -free 1 mM EGTA-containing solution, …
Microvascular Sex- and Age- Dependent Phosphodiesterase Expression
2021
Objective: The cyclic nucleotide second messengers, cAMP and cGMP, are pivotal regulators of vascular functions; their cellular levels are tightly controlled by the cyclic nucleotide hydrolases, phosphodiesterases (PDE). Biologic sex and age are recognized as independent factors impacting the mechanisms mediating both vascular health and dysfunction. This study focused on microvessels isolated from male and female rats before (juvenile) and after (adult) sexual maturity under resting conditions. We tested the hypothesis that sexual dimorphism in microvascular PDE expression would be absent in juvenile rats, but would manifest in adult rats.Methods: Abdominal skeletal muscle arterioles and v…
cGMP MODULATES STEM CELLS DIFFERENTIATION TO NEURONS IN BRAIN IN VIVO
2010
During brain development neural stem cells may differentiate to neurons or to other cell types. The aim of this work was to assess the role of cGMP (cyclic GMP) in the modulation of differentiation of neural stem cells to neurons or non-neuronal cells. cGMP in brain of fetuses was reduced to 46% of controls by treating pregnant rats with nitroarginine-methylester (L-NAME) and was restored by co-treatment with sildenafil.Reducing cGMP during brain development leads to reduced differentiation of stem cells to neurons and increased differentiation to non-neuronal cells. The number of neurons in the prefrontal cortex originated from stem cells proliferating on gestational day 14 was 715 +/- 14/…
ROLIPRAM INHIBITS PAF-INDUCED AIRWAY MICROVASCULAR LEAKAGE IN GUINEA-PIG - A COMPARISON WITH MILRINONE AND THEOPHYLLINE
1992
The effects of 3 phosphodiesterase (PDE) inhibitors, rolipram (PDE IV), milrinone (PDE III) and theophylline (non-selective) on PAF (50 ng kg-1; iv)-induced airway vascular leakage have been evaluated in guinea-pigs. Rolipram (3-300 micrograms kg-1; iv) reduced the increase in permeability induced by PAF at all airway levels whereas milrinone (10-1000 micrograms kg-1; iv) and theophylline (30 mg kg-1; iv) were without effects. The anti-leakage activity of rolipram may be of therapeutic value in asthma.
Pharmacological comparison of rat and human melanocortin 3 and 4 receptors in vitro.
2002
Abstract The melanocortin 3 and 4 receptors are G-protein-coupled receptors found in the hypothalamus with important role in regulation of the energy balance. In this study, we performed pharmacological comparison of the rat and human melancortin (MC) 3 and MC4 receptors. We transiently expressed the genes for these receptors individually in a mammalian cell line and determined the binding affinities to several MSH peptides. The results showed no major difference between the rat and human MC3 receptors while the rat MC4 receptor had higher affinity to several peptides compared with the human MC4 receptor. NDP-, α-, β-, γ-MSH, ACTH(1–24), HS014 and MTII had from 5- to 34-fold higher affinity…