Biomedical subjects
Publications and source records attributed to N Chand.
Metiamide (H2-histamine receptor antagonist) blocked histamine-induced relaxations and significantly potentiated contractile responses to histamine on isolated spiral strips of chicken ileum. This investigation showed the presence of H2-inhibitory receptors in chicken ileum.
Vascular (pulmonary and hepatic blood vessels) and nonvascular (gastro-intestinal, reproductive and respiratory systems) smooth muscle preparations obtained from specifically sensitized animals of numerous species including man contract to specific antigen in vitro (Schultz-Dale phenomenon). This immunopharmacological technique is a useful tool to demonstrate immediate-type hypersensitivity in actively or passively sensitized tissues and may be used to investigate the nature of the principal pharmacological mediators involved in a particular tissue as well as to screen anti-anaphylactic (anti-allergic) drugs. However, much remains to be investigated on the complex mechanisms of action of antigen, desensitization and resensitization (recovery) of anaphylactic responsiveness.
Histamine, 2-methylhistamine (a specific H1-agonist), 5-HT, PGF2alpha, SRS-A, bradykinin (BK) and carbachol contract bronchial and tracheal smooth muscles of the horse. Isoprenaline, PGE1, E2, dimaprit and 4-methylhistamine (last two = specific H2-agonists) relaxed airways which were partially contracted to carbachol. Mepyramine (a specific H1-antagonist) selectively antagonized contractions to histamine. In the presence of mepyramine, histamine caused relaxation of airways partially contracted to carbachol. Metiamide and burimamide (specific H2-antagonists) specifically antagonized or reversed histamine-induced bronchorelaxation. However the H2-antagonists, indomethacin and propranolol each failed to block histamine-induced relaxations in trachea. Thus, the results of this study show: (i) preponderence of H1-receptors-mediating contractions in horse airways; (ii) presence of H2-receptors-mediating bronchorelaxation and (iii) the existence of an atypical (relaxant) response (resistance to H2-antagonists; indomethacin and propranolol) in the horse trachea.
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Isolated chicken bronchus contracts to carbachol, PGF2alpha, histamine, 5-HT, bradykinin and phenylephrine. The bronchial strips from the horse plasma sensitized domestic fowl contracted to specific sensitizing antigen in vitro (Schultz-Dale anaphylactic reaction) and were 5 to 10 fold more reactive to PGF2alpha, histamine and 5-HT compared with the bronchi from normal chickens. Second antigen challenge was inactive or produced a weak response (desensitization). Allowing the bronchi to rest for 1 h resulted in partial recovery of anaphylactic response. Bronchi which had partially contracted submaximally to carbachol, antigen or PGF2alpha, relaxed to isoprenaline, adrenaline and PGE1 and E2.
Isolated chicken bronchus (which had been partially contracted to carbachol) relaxes to isoproterenol and epinephrine but contracts weakly to phenylephrine. Propranolol (a beta-adrenoceptor blocker) antagonizes isoproterenol and reverses epinephrine-induced relaxations to feeble contractions. Phenylephrine-induced bronchoconstrictions and constrictions to epinephrine (in the presence of beta-blockade) were blocked by phentolamine. The results of this study showed the predominance of beta-)inhibitory) adrenoceptors and some alpha-(excitatory) adrenoceptors in the bronchus of the adult domestic fowl.
The anti-anaphylactic effects of four potential anti-allergic agents (DSCG: disodium cromoglycate, PRD-92-EA, M&B 22,948 and DECC: diethylcarbamazine citrate) were studied on cardiovascular responses of acute systemic anaphylaxis and chemical mediators of immediate hypersensitivity in chickens. Compounds M&B 22,948, PRD-92-EA, DSCG and DECC all inhibited cardiovascular manifestations of systemic anaphylaxis in domestic fowl. High doses of Compounds PRD-92 EA, M&B 22,948 and DECC also exhibited a nonspecific receptor blocking activity towards exogenously administered chemical mediators of anaphylaxis.
Ferret trachea and bronchus contract to carbachol greater than 5-HT greater than bradykinin (BK) greater than PGF2alpha greater than histamine greater than 2-methylhistamine (2-MeH: a specific H1-receptor agonist). Rat trachea is insensitive to the spasmogenic actions of histamine, 2-MeH, PGF2alpha, BK and 5-HT. Ferret trachea and bronchus and rat trachea (which were partially contracted to carbachol) relax to isoproterenol greater than PGE1 greater than E2 greater than 4-methyl-histamine (4-MeH: a specific H2-histamine receptor agonist). High doses of histamine also relax rat trachea. The contractions of ferret airways to 2-MeH coupled with the antagonism of histamine-induced contractions by mepyramine showed the presence of H1-histamine receptors in the trachea and bronchus of ferret. After H1-blockade, the relaxant responses to histamine on ferret bronchus and trachea, and rat trachea were not affecte by "specific" doses of burimamide, metiamide, and cimetidine (H2-receptor antagonists), indomethacin (PG-synthetase inhibitor) and propranolol (a beta-adrenoceptor blocker). These results appear to suggest the existence of an atypical histamine receptor subtype (i.e. not of the classical H1 or H2 type) in the airways of rat and ferret.
Bovine albumin (BA: 2 mg/kg-1, i.v.) produced a fall in systemic arterial blood pressure accompanied by central venous hypertension and bradycardia in pentobarbital-anaesthetized, spontaneously breathing, bovine albumin-sensitized adult domestic fowl. Trasylol (a potent inhibitor of kallikreins) suppressed acute systemic anaphylaxis. Polyphloretin phosphate (an effective antagonist of PGF2alpha) also inhibited the cardiovascular responses to antigen and PGF2alpha. Sodium meclofenamate and phenylbutazone showed varying degree of blockade of cardiovascular responses to exogenously administered chemical mediators (bradykinik, PGF2alpha, SRS-A and to a lesser extent of histamine, 5-HT and acetylcholine) and antigen. Indomethacin (virtually devoid of receptor blocking activities toward exogenously injected chemical mediators) inhibited anaphylaxis. The results of this investigation strongly suggested an important role of vasoactive lipids and polypeptides in avian anaphylaxis.
Immunological release of histamine from the whole blood of the sensitized chickens was demonstrated. Compound 48/80 (a potent histamine releaser) released histamine from isolated chicken lung. The sensitizing antigens (bovine albumin or horse plasma) did not release histamine from the lung. Bovine albumin and horse plasma released slow-reacting substance of anaphylaxis only from the lungs of adult domestic fowl and not from ileum or lungs of immature chickens.
Histamine, 2-methylhistamine (2-MeH: a relatively specific H1 receptor agonist), 5-HT, carbachol, bradykinin (BK) and PGF2alpha contract isolated cat pulmonary vein, artery and hepatic vein. PGE1, PGF2alpha and 4-methylhistamine (4-MeH: a relatively specific H2-receptor agonist) contract pulmonary arterial strips but further increase in the dose of PGE1 produces relaxation. Isoproterenol relaxes partially contracted blood vessels at low doses, but contracts at high doses. Cat trachea contracts to 5-HT, acetylcholine and carbachol but is insensitive to histamine, its analogues, BK and PGF2alpha. However, partially contracted trachea relaxes to histamine, 4-MeH, 2-MeH, isoprenaline, BK, PGE1, E2 and F2alpha. PGF2alpha and SRS-A contract cat bronchus. Isoprenaline, PGE1 and E2 relax cat bronchus contracted to carbachol, 5-HT, PGF2alpha, SRS-A and antigen. The in vitro anaphylactic contraction (Schultz-Dale reaction) of isolated pulmonary and hepatic veins, bronchus and trachea from horse plasma sensitized cat suggested the involvement of lung and liver in anaphylaxis of the cat.
A chronically azotemic 2 6/12 boy developed diffuse, bilateral pulmonary calcification. The radiographic features and pathologic mechanism of such pulmonary calcification is discussed.
Histamine, 2-methylhistamine (a specific H1-receptor agonist), 4-methylhistamine (a specific H2-receptor agonist), isoprenaline, bradykinin, prostaglandin E1, E2, and F 2alpha induce relaxation of carbachol-contracted isolated cat bronchial strips and tracheal chains. Bovine SRS-A contracts bronchus but not trachea. Histamine-induced relaxation of cat bronchus is not blocked by mepyramine (a specific H1-receptor antagonist); metiamide or burimamide (specific H2-receptor antagonists); propranolol ( a beta-adrenoceptor blocker) and indomethacin (a PG-synthetase inhibitor) suggesting non-participation of H1,H2-histamine receptors, beta-adrenoceptors (catecholamine release) and prostaglandin release in histamine-induced broncho-relaxations in the cat. The existence of an atypical histamine response, resistant to both H1- and H2-receptor antagonists is thus established in cat bronchus.
1 Isolated pulmonary arterial and vein strips from sensitized or non-sensitized chickens exhibited dose-dependent contractions to adrenaline greater than, noradrenaline greater than, 5-hydroxytryptamine greater than, histamine greater than, dopamine. Individual variability in the responsiveness of the vessels to agonists was marked. In general veins were 2 to 25 times more sensitive to agonists than arterial strips. 2 Isoprenaline (a relatively specific beta-adrenoceptor agonist) induced relaxation of the submaximally contracted pulmonary vein and arteries at low doses and contractions at high concentrations. 3 Contractile responses to acetylcholine or carbachol were not regularly recorded; only 50% of the vessels reacted to cholinoceptor agonists over a wide threshold dose range. 4 Chicken pulmonary vessels were found relatively insensitive to bradykinin. 5 Effects of prostaglandins were variable. Prostaglandin F2alpha induced dose-related contractions of the vein and arterial strips; prostglandins E1 and E2 at low doses partially contracted pulmonary artery irrespective of the spasmogen used and further increase in doses induced either no effect or contractions. Prostaglandin E1 induced marked and rapid contractions of the vein. Prostaglandin E2 induced relaxations of the prostaglandin F2alpha-contracted vein only, but produced no effect or slight contractions of the veins partially contracted to other spasmogens. 6 Pulmonary arterial and vein strips obtained from chickens sensitized to horse plasma exhibited Schultz-Dale contractions of variable magnitude and duration to specific antigenic challenge only. In many vessels, antigen-induced contractions were associated with marked increase in spontaneous activity. 7 The importance of the Schultz-Dale reaction in avian pulmonary vessels is discussed in relation to the right heart dilatation associated with anaphylaxis in the chicken.
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Nonsteroidal anti-inflammatory drugs inhibit the biosynthesis of kinins and prostaglandins and stabilize leukocyte lysosomal membranes. Nonsteroidal anti-inflammatory drugs also weakly block the biosynthesis of histamine and serotonin, and pharmacologically antagonize kinins, prostaglandins and slow-reacting substance of anaphylaxis. Nonsteroidal anti-inflammatory drugs effectively control both cardiovascular and respiratory manifestations of hypersensitivity in cattle and horses. This, coupled with the contrasting lack of effectiveness of "antiamine" drugs, suggests that bio-amines such as histamine and serotonin (5-hydroxytryptamine) may be less important than kinins, postaglandins and slow-reacting substance in the mediation of the hypersensitivity/inflammatory reaction, at least in cardiopulmonary systems of these species. Nonsteroidal anti-inflammatory drugs justify more prominence in the clinical control of acute respiratory disease in domestic herbivores.
1 The Schultz-Dale phenomenon has been demonstrated in several circular smooth muscle strips of oesophagus, crop, duodenum, jejunum and ileum taken from young and adult domestic fowl sensitized actively to crystalline bovine albumin or horse plasma. 2 The ileal strips contract to acetylcholine, histamine, 5-hydroxytryptamine (5-HT), prostaglandins E1, E2, F2alpha, bradykinin and bovine slow reacting substance of anaphylaxis (SRS-A). Marked seasonal and individual variations in the responsiveness of gut tissues to these exogenous agonists were noted. 3 Antagonism of contractions to histamine by mepyramine suggests the existence of H1-histamine receptors in chicken ileum. Blockade of 5-HT-induced contractions by methysergide shows the preponderance of 'D'-musculotropic tryptamine receptors. 4 Failure of selective receptor antagonists of acetylcholine, histamine and 5-HT to modify the Schultz-Dale reaction suggests the nonparticipation of aminergic mechanisms in this reaction. 5 Partial to complete blockade of the Schultz-Dale reaction by a prostaglandin receptor antagonist (polyphloretin phosphate, PPP); prostaglandin synthetase inhibitors (sodium meclofenamate and phenylbutazone); inhibitors of synthesis and release of histamine and SRS-A (PR-D-92-EA, M & B 22948, diethylcarbamazine citrate, and PPP) and an inhibitor of proteinases (aprotinin) strongly suggests the involvement of vasoactive lipids and polypeptides in the anaphylactic response of chicken ileum to specific antigen.