thiourea and Hypersensitivity

The in vivo role of nitric oxide in inflammatory cell migration, vascular permeability and the development of hyperresponsiveness to methacholine (MCh) was studied in rats 24 h following ovalbumin (OVA) challenge. The NO synthase (NOS) inhibitors N(G)-mono-methyl-L-arginine (L-NMMA; nonselective), aminoguanidine (two-fold inducible NOS-selective), N(omega)-nitro-L-arginine methyl ester (L-NAME; 2000-fold endothelial cell NOS-selective) or S-methyl-L-thiocitrulline (100-fold neuronal NOS-selective) were administered (100 mg x kg(-1) s.c.) to OVA-sensitized Piebald-Virol-Glaxo rats on 3 consecutive days during which they were challenged with allergen (1% OVA). Responses to inhaled MCh were measured in anaesthetized animals 24 h after OVA challenge. Cellular inflammation and vascular permeability were assessed using bronchoalveolar lavage (BAL) fluid collected 30 min after administration of Evans blue (50 mg x kg(-1) i.v.). OVA challenge in sensitized animals induced hyperresponsiveness to MCh, inflammatory cell influx and increased leakage of Evans blue into the BAL fluid (n=9, p<0.001). Aminoguanidine was effective in inhibiting the allergen-induced cellular influx and microvascular leakage (n=9, p<0.001) without altering responses to MCh. This effect was reserved by L-arginine. L-NAME (n=5, p<0.01) and S-methyl-L-thiocitrulline (n=6, p<0.001) further potentiated the allergen-induced hyperresponsiveness without altering cellular inflammation. L-NMMA attenuated both the OVA-induced cellular influx and Evans blue leakage (n=8, p<0.001) as well as further potentiating the hyperresponsiveness to MCh (p<0.05). From these studies, it is suggested that, in allergic Piebald-Virol-Glaxo rats, nitric oxide production by inducible nitric oxide synthase plays a role in the migration of inflammatory cells and increase in vascular permeability following allergen challenge, whereas nitric oxide produced by the constitutively expressed neuronal nitric oxide synthase limits hyperresponsiveness to methacholine.

Topics: Animals; Bronchoalveolar Lavage Fluid; Bronchoconstrictor Agents; Citrulline; Disease Models, Animal; Enzyme Inhibitors; Guanidines; Hypersensitivity; Male; Methacholine Chloride; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; omega-N-Methylarginine; Rats; Thiourea

The cyclization of ethyl 2-benzoylthioureidothiophen-3-carboxylates under basic conditions is known to give 2-thioxothieno[2,3-d]pyrimidin-4(1H, 3H)-ones. On the other hand, we have found that ethyl 2-benzoylthioureidothiophen-3-carboxylates 10-16 on treatment with concentrated sulphuric acid or polyphosphoric acid/ethanol undergo cyclization to give the new 2-aminothieno[2,3-d][1,3]thiazin-4-ones 17-23, in some cases 5,6-anellated. Reaction of 10-16, which are readily available from ethyl 2-aminothiophen-3-carboxylates 3-9 and benzoyl isothiocyante affords the title compounds 17-23 in good yields. Mass spectral fragmentation of 17-23 is discussed. A series of 2-aminothieno[2,3-d][1,3]thiazin-4-ones, which contain a free or substituted amino group was evaluated in the rat active cutaneous anaphylaxis test for anti-allergy activity. One compound, 23 had weak activity in the range of theophylline. Only high concentrations of this compound inhibited weakly the histamine release from rat peritoneal mast cells activated by protamine sulfate.

Topics: Animals; Chemical Phenomena; Chemistry; Female; Histamine Release; Hypersensitivity; Lipoxygenase Inhibitors; Mast Cells; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred Strains; Spectrophotometry, Ultraviolet; Thiazines; Thiophenes; Thiourea

Topics: Basophils; Cyclic AMP; Diphenhydramine; Feedback; Histamine; Histamine H1 Antagonists; Histamine Release; Humans; Hypersensitivity; Imidazoles; Leukocytes; Receptors, Drug; Thiourea

Topics: Animals; Guinea Pigs; Hyperemia; Hypersensitivity; Microbial Sensitivity Tests; Skin Tests; Thiocyanates; Thiourea

Topics: Hypersensitivity; Hyperthyroidism; Iodides; Iodine; Iodine Isotopes; Thiourea

Topics: Anaphylaxis; Hypersensitivity; Immune System Diseases; Thiourea

Topics: Anaphylaxis; Hypersensitivity; Immune System Diseases; Shock; Thiourea