On the mechanism of histamine-induced bronchodilation in conscious guinea-pigs

Abstract

The bronchodilatory effect of histamine was evaluated in a conscious guinea-pig model of cholinergically mediated bronchoconstriction. The H1, bronchoconstrictor, property of histamine was masked using high doses of the H1-antagonist chlorpheniramine (30 mg/kg), and the bronchodilatory activity evaluated by observing the increase in latency to collapse induced by aerosol methacholine. Under these conditions, histamine (1.0, 3.0 or 10.0 mg/kg, i.p.) delayed methacholine-induced collapse in a dose-dependent manner. Cimetidine, an H2-receptor antagonist (10 to 100 mg/kg), did not delay collapse either in the presence or absence of an H1-antagonist. However, when cimetidine was administered prior to histamine, the bronchodilatory activity of histamine was abolished. A similar abolition of histamine bronchodilation was observed if propranolol, a beta-adrenoceptor antagonist, was administered prior to histamine. Propranolol alone had no effect on methacholine-induced bronchospasm. These data suggest that the major bronchodilatory property of histamine may be mediated indirectly via catecholamine release through an H2-receptor mechanism.

Differential in vivo and in vitro bronchorelaxant activities of CP-80,633, a selective phosphodiesterase 4 inhibitor

“…In these studies, an infusion of histamine was used to increase R L . Histamine alone causes the release or elevation of catecholamines (Williams et al 1984;Schellenberg et al 1991). Consistent with these observations, catecholamine levels were elevated by histamine infusion in our experiments, but a bronchodilatory dose of CP-80,633 (10 µg/kg) did not cause a further Note: E max and EC 50 values are means ± SEM.…”

Pharmacokinetics of R(–) and S(+) carprofen after administration of racemic carprofen in donkeys and horses

“…There is an increasing body of data that suggests that there are important pharmacokinetic and pharmacodynamic differences between enantiomers of NSAIDs, despite the fact that clinically used drugs are typically racemic agents. [7][8][9] The S(+) enantiomer of carprofen is primarily responsible for the drug' s pharmacologic effects. 10 Therefore, it is important that enantiomeric forms are distinguished in pharmacokinetic studies of NSAIDs.…”