Inhibition of compound 48/80 ? induced vascular protein leakage by pretreatment with capsaicin and a substance P antagonist

Abstract

Intravenous injection of compound 48/80 (1 mg X kg-1) induced an acute increase in vascular permeability to plasma proteins in various organs of rats. The compound 48/80 response was partly inhibited by histamine H1 and H2 receptor blockade in the urinary bladder and in the duodenum, but not in the trachea, the oesophagus, the ureter and the paw skin. Blockade of 5-hydroxytryptamine receptors with methysergide led to a reduction of the permeability response in the oesophagus and in the urinary bladder, leaving responses in other organs unchanged. Pretreatment of neonatal rats with capsaicin almost abolished the 48/80 response in all organs except in the duodenum. Pretreatment of rats with [D-Arg1, D-Trp7,9, Leu11]-substance P, a substance P antagonist, also caused a partial inhibition of the permeability response to compound 48/80 in several organs. Topical administration of compound 48/80 (1 mg X ml-1) onto the tracheal mucosa induced local Evans blue extravasation. This response was resistant to pretreatment with histamine receptor antagonists, but was largely inhibited after neonatal capsaicin pretreatment. Topical administration of compound 48/80 (1 mg X ml-1 or 10 mg X ml-1) into the eye did not cause visible Evans blue extravasation in the conjunctiva, nor any signs of pain reaction as indicated by the absence of the wiping response, usually seen upon noxious chemical stimuli in the eye. In guinea-pigs, 10 mg X kg-1 compound 48/80 i.v. were required to induce vascular protein leakage in different organs. This response was blocked by pretreatment with H1 and H2 receptor antagonists, but only slightly reduced after systemic capsaicin pretreatment of guinea-pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice

“…on both blood vessels and neurons, via interactions with their respective receptors. In fact, C48/80 effects can be significantly inhibited by antagonists of histamine H1 receptors, 5-HT or substance P (NK1) receptors [36,46,47].…”

Role of histamine in the development of neurogenic inflammation of rat oral mucosa

“…Effect of various histamine-receptor antagonists on the neurogenic inflammatory reaction appeared to vary according to organs tested. Thus, the administration of H 1 and H 2 receptor antagonists partially prevented the neurogenically induced augmentation of blood flow and vascular permeability in the mucosal tissue of the urinary bladder but the same histamine antagonists were ineffective in the esophagus and ureter [26]. These results seem to indicate that histamine release may play different role in the mechanism of the neurogenic inflammatory responses in various organs.…”

Inhibition of hind-paw edema and cutaneous vascular plasma extravasation by 2-chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D1) in mice

“…Polymyxin B-induced hind-paw edema is mediated by prostaglandins and mast cell-released mediators (Bertelli and Soldani 1979;Wang et al 1992). Mast cells release chemical mediators such as histamine and serotonin, which in turn increase vascular permeability and plasma exudation from the nearby microvasculature in the passive cutaneous anaphylactic reaction and in compound 48/80 challenge (Saria et al 1983(Saria et al , 1984. Since indomethacin has no effect on the plasma exudation in response to compound 48/80 and in the passive cutaneous anaphylactic reaction (Taira et al 1988;Wang et al 1994), the inhibition by PP1D1 of the edematous responses caused by polymyxin B, compound 48/80 and anaphylaxis was not mainly through inhibition of the prostaglandin pathway.…”