Search results for "clic"

3H-cyproterone acetate: binding characteristics to human uterine progestagen receptors

1985

The availability of tritium labeled cyproterone acetate (CPA) facilitated the systematic investigation of the binding characteristics of this compound for human uterine progesterone receptors (PgR). The binding parameters of 3H-CPA are compared to those of 3H-R5020 and 3H-progesterone. The rate constants of association (k1M-1sec-1) to PgR were 7.8 X 10(3) for 3H-R5020, 4.5 X 10(4) for 3H-progesterone and 4.0 X 10(4) for 3H-CPA. The rate constants of dissociation (k-1, sec-1) were 3.6 X 10(-5) for 3H-R5020, 21.3 X 10(-5) for 3H-progesterone and 17.8 X 10(-5) for 3H-CPA. The Kd-values (M), as obtained by titration analysis and subsequent Scatchard plot analysis were 1.2 X 10(-9) for 3H-R5020,…

Characteristics of histamine tachyphylaxis in rat uterine smooth muscle.

2002

Objective and design: To study both the desensitisation induced by short-term exposure to histamine and the mechanism responsible in the isolated rat uterus.¶Material: Precontracted isolated uterus (37 mM KCl) from oestrogenised Wistar rats were used.¶Treatment: Repetitive responses to histamine (10–6, 10–5, 10–4, 10–3 M), dimaprit and clonidine (10–4 M) were tested at 15, 30, 45 and 105 min., with their modifications by (5 mg/ kg, 24 h before sacrifice) reserpine, 10–7 M propranolol, 10–8 M atropine, and 10–6 M indomethacin. Dose-response curves for adrenaline were carried out as standard protocol.¶Methods: In vitro techniques (de Jalon's solution, 31°C, carbogen, isotonic registration, re…

Adrenergic Stimulation of Cyclic GMP Formation Requires NO-Dependent Activation of Cytosolic Guanylate Cyclase in Rat Pinealocytes

1993

Cyclic GMP (cGMP) formation in rat pinealocytes is regulated through a synergistic dual receptor mechanism involving beta- and alpha 1-adrenergic receptors. The effects of NG-monomethyl-L-arginine (NMMA), which inhibits nitric oxide (NO) synthase and NO-mediated activation of cytosolic guanylate cyclase, and methylene blue (MB), which inhibits cytosolic guanylate cyclase, were investigated in an attempt to understand the role of NO in adrenergic cGMP formation. Both NMMA and MB inhibited beta-adrenergic stimulation of cGMP formation as well as alpha 1-adrenergic potentiation of beta-adrenergic stimulation of cGMP formation, whereas they had no effect in unstimulated pinealocytes. The inhibi…

Cloning of two melanocortin (MC) receptors in spiny dogfish

2004

We report the cloning and characterization of two melanocortin receptors (MCRs) from the spiny dogfish (Squalus acanthias) (Sac). Phylogenetic analysis shows that these shark receptors are orthologues of the MC3R and MC5R subtypes, sharing 65% and 70% overall amino acid identity with the human counterparts, respectively. The SacMC3R was expressed and pharmacologically characterized in HEK293 cells. The radioligand binding results show that this receptor has high affinity for adrenocorticotropic hormone (ACTH)-derived peptides while it has comparable affinity for alpha- and beta-melanocyte stimulating hormone (MSH), and slightly lower affinity for gamma-MSH when compared with the human ortho…

Inhibition of ovarian steroidogenesis by cyclic-GMP in a fly

2003

1479-6805 0022-0795; Previous investigations in the female blowfly Phormia regina have shown that 3-isobutyl-1-methylxanthine (IBMX), a broad spectrum inhibitor of phosphodiesterases (PDEs), fails to mimic the steroidogenic effects of cAMP on ovaries, although it efficiently increases the concentrations of this second messenger. In this study, experiments carried out to clear up this contradiction demonstrated that IBMX, besides its effect on cAMP, also increased cGMP concentrations in blowfly ovary and that these two cyclic nucleotides controlled ovarian steroidogenesis antagonistically. In particular, a selective inhibitor of cGMP-specific PDEs, unlike IBMX, had a very strong negative eff…

Phosphodiesterase-4 inhibition improves corticosteroid insensitivity in pulmonary endothelial cells under oxidative stress.

2012

Several clinical studies have shown that smoking in asthmatics and chronic obstructive pulmonary disease patients is closely associated with corticosteroid refractoriness. In this work, we have analyzed glucocorticoid insensitivity in human pulmonary artery endothelial cells (HPAECs) under cigarette smoke extract (CSE) exposure as well as the possible additive effects of the combination therapy with a phosphodiesterase (PDE)-4 inhibitor. Interleukin (IL)-8 was measured in cell supernatants by ELISA. Histone deacetylase (HDAC), histone acetylase (HAT), and intracellular cAMP levels were measured by colorimetric assays and enzyme immunoassay, respectively. PDE4 isotypes and glucocorticoid rec…

Cardiovascular Events in Rheumatoid Arthritis-Time to See Beyond Articular Involvement in "Real World" Clinical Practice: Comment on the Article by M…

2015

The phototransduction cascade in the isolated chick pineal gland revisited.

2003

It is well established that the isolated chick pineal gland is directly light sensitive and that melatonin synthesis of the gland can be inhibited by exposing the gland to light during scotophase. Since not all the steps of the phototransduction cascade have been clarified to the same extent as in the retina, we have treated isolated chick pineal glands with 90 min of light during scotophase and with drugs that affect key-components of vertebrate phototransduction, i.e., cyclic guanosine monophosphate (cGMP) phosphodiesterase 6 (PDE6), cGMP levels and cGMP-gated calcium channels. The endpoint measured was the activity of the rate-limiting enzyme of melatonin synthesis, arylalkylamine N-acet…

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…