cyclic-gmp and Hypersensitivity

Nitric oxide (NO) plays diverse roles in physiological and pathological processes. During immune and inflammatory responses, for example in asthma, NO is generated at relatively high and sustained levels by the inducible form of nitric oxide synthase (NOS-2). NOS-2 derived NO regulates the function, growth, death and survival of many immune and inflammatory cell types. In the case of mast cells, NO suppresses antigen-induced degranulation, mediator release, and cytokine expression. The action of NO on mast cells is time dependent, requiring several hours, and noncGMP mediated, most probably involving chemical modification of proteins. NO inhibits a number of mast cell-dependent inflammatory processes in vivo, including histamine mediated vasodilatation, vasopermeation and leucocyte-endothelial cell attachment. In human asthma and animal models of lung inflammation the role of NO is harder to define. However, although there are conflicting data, the balance of evidence favours a predominantly protective role for NO. Mimicking or targeting NO dependent pathways may prove to be a valuable therapeutic approach to mast cell mediated diseases.

Topics: Animals; Asthma; Cyclic GMP; Cytokines; Cytoplasmic Granules; Disease Models, Animal; Endopeptidases; Heparin; Histamine Release; Humans; Hypersensitivity; Inflammation; Mast Cells; Mice; Mice, Knockout; Models, Biological; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress; Signal Transduction; Swine

Classic allergic reactions of the immediate type are IgE dependent. These reactions are associated with a complex orchestration of genetic predisposition, allergen exposure patterns, allergen processing by mononuclear macrophages, helper and suppressor immunocytes, pharmacologically active inflammatory mediators, early and late-phase reactions, neurotransmitters, autonomic nervous system participation, intracellular cyclic nucleotide equilibrium, cellular and molecular activity, and a genetically predetermined end-organ hypersensitivity to a variety of specific and nonspecific excitants.

Topics: Autonomic Nervous System; B-Lymphocytes; Cyclic AMP; Cyclic GMP; Humans; Hypersensitivity; Immunoglobulin E; Mast Cells; Reagins; T-Lymphocytes

Topics: Animals; Ascorbic Acid; Candida albicans; Cell Division; Chemotaxis, Leukocyte; Copper; Cyclic GMP; Extracellular Matrix; Extracellular Space; Histamine; Horseradish Peroxidase; Humans; Hydrogen Peroxide; Hypersensitivity; Immunization; Inflammation; Iodides; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Phagocytosis; Prostaglandins; SRS-A

Topics: Adenylyl Cyclases; Adult; Asthma; Calcium; Child; Cromolyn Sodium; Cyclic AMP; Cyclic GMP; Dermatitis, Atopic; Humans; Hypersensitivity; Immunoglobulin E; Muscle, Smooth; Phosphodiesterase Inhibitors

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Calcium; Chemotaxis; Cyclic AMP; Cyclic GMP; Diabetes Insipidus; Glycogen; Humans; Hypersensitivity; Intestinal Mucosa; Lipid Metabolism; Lymphocytes; Methods; Mice; Neoplasms; Nucleotides, Cyclic; Parathyroid Diseases; Phagocytosis; Rats

Topics: Animals; Antibody Formation; B-Lymphocytes; Cyclic AMP; Cyclic GMP; Cytotoxicity Tests, Immunologic; Humans; Hypersensitivity; Immunity, Cellular; Immunosuppression Therapy; Indomethacin; Inflammation; Lymphocyte Activation; Lymphocytes; Macrophages; Neoplasms; Neutrophils; Prostaglandins; Receptors, Prostaglandin; T-Lymphocytes

Topics: Adrenal Cortex Hormones; Adrenergic alpha-Agonists; Atropine; Bronchi; Cromolyn Sodium; Cyclic AMP; Cyclic GMP; Histamine H1 Antagonists; Humans; Hypersensitivity; Metabolism; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Prostaglandins; Sympathomimetics

Topics: Adrenergic beta-Antagonists; Allergens; Allergy and Immunology; Asthma; Austria; Autonomic Nervous System; Bronchodilator Agents; Cyclic AMP; Cyclic GMP; Emotions; Expectorants; Histamine Release; History, 20th Century; Humans; Hypersensitivity; Hypersensitivity, Delayed; Lymphokines; Phosphates; Phosphoric Diester Hydrolases; Potassium Iodide; Prostaglandins; Reflex; Respiratory Tract Infections; SRS-A; Temperature; United States

The sensitivity of animals to endotoxin differs significantly between species. Thus, factors that determine the susceptibility to endotoxin may play important roles in the pathogenesis of septic shock. In order to determine the mechanism responsible for susceptibility to endotoxin, the effect of lipopolysaccharide (LPS) on the circulatory status of Propionibacterium acnes (PA)-sensitized rats was studied. Following the intravenous administration of a low dose of LPS, the arterial blood pressure of PA-treated rats, but not of normal animals, progressively decreased; the PA-sensitized animals died of circulatory shock within 7 h of LPS administration. N omega-nitro-L-arginine (NA) reduced the depressor effect of LPS by an L-arginine-inhibitable mechanism. Administration of LPS markedly increased the level of the inducible type of nitric oxide (NO) synthase in various tissues, including the aorta, of PA-treated rats but not of control animals. LPS also increased plasma levels of nitrate plus nitrite and aortic levels of cGMP. Dexamethasone inhibited the de novo synthesis of NO synthase in the aorta and other tissues and reduced the depressor effect of LPS. These and other findings suggest that induction of nitric oxide synthase in resistant arteries might underlie the pathogenesis of LPS-induced hypotension in PA-sensitized animals and the mechanism responsible for the susceptibility to endotoxin.

Topics: Amino Acid Oxidoreductases; Animals; Aorta; Arginine; Blood Pressure; Cyclic GMP; Dexamethasone; Enzyme Induction; Heart Rate; Hepatectomy; Hypersensitivity; Lipopolysaccharides; Male; Nitrates; Nitric Oxide Synthase; Nitrites; Nitroarginine; Propionibacterium acnes; Rats; Rats, Wistar; Shock, Septic; Splenectomy; Survival Analysis; Tissue Distribution

Topics: Acetylcholine; Animals; Blood Platelets; Cyclic GMP; Free Radicals; Guanylate Cyclase; Heart; Histamine; Hypersensitivity; Myocarditis; Myocardium; Rabbits; Solubility

The effects of 11-oxo-11H-pyrido[2,1-b]-quinazoline-2-carboxylic acid (Sm 857), a new antiallergic drug, on histamine release from human leukocytes and from human and monkey lungs were investigated. Sm 857 dose-dependently inhibited histamine release induced by mite antigen, anti-human IgE, calcium ionophore A23187 (A23187) and protein A from peripheral leukocytes of atopic patients, but had no effect on the levels of cyclic AMP and GMP in human leukocytes. In addition, antigen- or anti-human IgE-induced anaphylactic histamine release from human and monkey lung fragments passively sensitized with human reaginic serum sensitive to mite antigen as well as A23187-induced histamine release from non-sensitized monkey lung fragments, were inhibited dose-dependently by Sm 857. However, no inhibition of spontaneous histamine release from human leukocytes or monkey lung fragments by Sm 857 was observed.

Topics: Animals; Calcimycin; Cyclic AMP; Cyclic GMP; Histamine Release; Humans; Hypersensitivity; Leukocytes; Lung; Macaca; Mites; Quinazolines

Topics: Asthma; Cyclic AMP; Cyclic GMP; Humans; Hypersensitivity; Receptors, Adrenergic, beta

The authors studied urine excretion of cyclic-AMP and cyclic-GMP in normal and allergic children before and after hyposensitization to house dust. The cyclic-AMP excretion was found to b diminished in the asthmatic group before the treatment. The hyposensitization did not modify these low levels. No significant variation of cyclic-GMP excretion was found among the normal, ante or post-hyposensitization asthmatic groups.

Topics: Asthma; Child; Child, Preschool; Creatinine; Cyclic AMP; Cyclic GMP; Desensitization, Immunologic; Female; Humans; Hypersensitivity; Male; Time Factors

Topics: Acute Disease; Adrenergic beta-Antagonists; Antigen-Antibody Reactions; Asthma; Bronchi; Cyclic AMP; Cyclic GMP; Histamine Release; Humans; Hypersensitivity; Muscle Contraction; Muscle, Smooth; Prostaglandins; Receptors, Drug; SRS-A

Topics: Asthma; Bronchi; Cyclic AMP; Cyclic GMP; Humans; Hypersensitivity; Irritants; Muscle Tonus; Muscle, Smooth; Receptors, Adrenergic; Receptors, Cholinergic