0000000000357065
AUTHOR
Josep Bou
Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus.
1. We have investigated the role of cyclic nucleotide phosphodiesterase IV (PDE IV) in the relaxation of human bronchus and guinea-pig trachea in vitro and in guinea-pigs in vivo. 2. Functional studies showed that the selective PDE IV inhibitors, rolipram and denbufylline, relaxed human and guinea-pig preparations in vitro. 3. Two clinically used xanthine non-selective PDE inhibitors, theophylline and pentoxifylline, were also effective in these preparations, but were much less potent than the selective agents used. 4. The rank order of potency for the four PDE inhibitors in both species was similar. 5. Biochemical studies indicated that PDE IV was the major PDE isoform present in the human…
Rolipram inhibits airway microvascular leakage induced by platelet-activating factor, histamine and bradykinin in guinea-pigs.
Abstract Rolipram (0·1–1000 μg kg−1, i.v.) reduced the increase in microvascular permeability induced by platelet-activating factor (PAF; 50 ng kg−1, i.v.) at different sites of the guinea-pig airways. Rolipram (1–100μg kg−1, i.v.) inhibited histamine (30μg kg−1, i.v.)-and bradykinin (0·3 μg kg, i.v.)-induced airway microvascular leakage. These effects of rolipram were obtained at doses which inhibit histamine (7–20 μg kg−1 min−1)-induced bronchoconstriction (IC50 = 3 ± 1 μg kg, i.v.) without depressing arterial blood pressure in the guinea-pig. Aminophylline (50 mg kg−1) did not change the effect of PAF. The anti-exudative effect of rolipram is of potential therapeutic value in asthma.
Characterization of 5-HT receptors on human pulmonary artery and vein: functional and binding studies
1. This study aimed to investigate the 5-hydroxytryptamine (5-HT) receptors mediating contraction of ring preparations isolated from human pulmonary arteries and veins. In functional studies, the responses to 5-HT, sumatriptan, ergotamine, serotonin-O-carboxymethyl-glycyl-tyrosinamide (SCMGT), alpha-methyl 5-HT (alpha-Me) and 2-methyl 5-HT (2-Me) were studied with WAY100635, GR127935, ritanserin, zacopride and SB204070 as antagonists. 2. All agonists produced concentration-dependent contractions of human pulmonary artery and vein preparations. The order of potency (-log ECS0 values) was ergotamine (6.88) > 5-HT (6.41) > or = SCMGT (6.20) = sumatriptan (6.19) > or = alpha-Me (6.04) in the ar…