Diana M. Temple

Loratadine, and antihistamine, blocks antigen- and ionophore- induced leukotriene release from human lung in vitro

Some H1-antihistamines possess anti-allergic properties, and inhibit the immunological release of mediators including histamine and sulfiopeptide-leukotrienes (slow reacting substance of anaphylaxis) from lung. The effects of the antihistiamine loratadine, SCH29851, on the release of leukotrienes and histamine from human lung fragments were measured, using the calcium ionophore A23187 and an extract of antigen from Dermatophagoides pteronyssinus, house dust mite, (with passively sensitized lung) as releasing agents. Loratadine (1-20 microM) inhibited the release of leukotrienes in a concentration-dependent manner when release was induced by calcium ionophore from lung specimens from 8 subjects, and also when release was induced by antigen from lung specimens from 7 subjects. Histamine release was unaffected by these concentrations of loratadine in both types of experiment.

Effect of fenoterol on immunological release of leukotrienes and histamine from human lung in vitro: Selective antagonism by β-adrenoceptor antagonists

The inhibitory effects of fenoterol, a beta 2-adrenoceptor agonist, on the release of SRS-A leukotrienes and histamine from chopped human lung tissue were measured and selective beta-adrenoceptor antagonists used to investigate the nature of the receptors involved. Fenoterol 0.01-1.0 microM inhibited the antigen-induced release of SRS-A and histamine, but not the release induced by the calcium ionophore A23187. Propranolol 0.1 and 1.0 microM and butoxamine 10 and 100 microM significantly antagonized the effects of fenoterol 0.1 microM on SRS-A and histamine at concentrations which affect (beta 2-adrenoceptors, while atenolol 0.1 to 10 microM showed no antagonism at concentrations which affect beta 1-adrenoceptors. These results suggest that adrenoceptors in human lung which modulate the immunological release of SRS-A leukotrienes are of the beta 2-subtype as for histamine release.

Effect of lipoxygenase inhibitors on release of slow-reacting substances from human lung

Abstract The effects of the lipoxygenase inhibitors nordihydroguaiaretic acid (NDG) and 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW 755C) on the release of slow-reacting substances (SRS) from human lung tissue were investigated in vitro. NDG (5 × 10 −6 M and 5 × 10 −5 M) and BW 755C (10 −5 and 10 −4 M) caused a dose-dependent inhibition of SRS release. There was a small reduction of histamine release with the higher concentration of each drug. These results suggest that lipoxygenase iny be useful in determining the role of SRS in inflammatory processes in vivo.

The effects of non-steroidal inhibitors of phospholipase Az on leukotriene and histamine release from human and guinea-pig lung

The effects of chloroquine and mepacrine were determined on the release of slow reacting substances (leukotrienes) from lung fragments in vitro. These drugs have been shown in a variety of tissues to inhibit phospholipase A2, and thus to reduce the availability of arachidonate, which is a substrate for leukotriene biosynthesis. Leukotriene and histamine release from unsensitized human lung was stimulated by calcium ionophore A23187, and from actively sensitized guinea-pig lung, by ovalbumin. Chloroquine (10 microM and 100 microM) significantly inhibited leukotriene release in lung from both species, and at 100 microM also inhibited histamine release. Mepacrine (10 microM) inhibited leukotriene release in human lung and at 100 microM in guinea-pig lung. The effects of chloroquine (100 microM) on leukotriene release were counteracted by the presence of arachidonic acid (10 microM), which suggests that chloroquine had impaired the availability of arachidonate. It seems probable that chloroquine and mepacrine inhibit leukotriene release by inhibition of phospholipase A2 in lung.

β-phenylethylamine as a cardiotonic constituent of tissue extracts

Abstract 1. 1. The cardiac stimulant substance ‘splenitransin’ in purified extracts of blood and spleen has been identified as β-phenylethylamine hydrochloride. 2. 2. A small proportion of this compound in extracts could have been produced as an artefact by decarboxylation of phenylalanine in hot solvents. 3. 3. However, β-phenylethylamine was detected also in extracts produced using low temperature conditions while a parallel phenylalanine control was not decarboxylated. 4. 4. A possible physiological role for β-phenylethylamine is suggested.

THE MEDIATORS OF ALLERGIC CONTRACTION OF HUMAN AIRWAY SMOOTH MUSCLE: A COMPARISON OF BRONCHIAL AND LUNG PARENCHYMAL STRIP PREPARATIONS

1. Antigen‐induced contractions of passively sensitized preparations of human bronchi and lung parenchymal strips were studied.

The antagonism by anti-inflammatory analgesics of prostaglandin F2α-induced contractions of human and rabbit myometrium in vitro

The anti-inflammatory analgesic drugs, aspirin, indomethacin, phenylbutazone, mefenamic acid ibuprofen and flurbiprofen are shown to inhibit in a dose-dependent manner the force of contraction of isolated human pregnant myometrial strips which have been stimulated to contract by adding prostaglandin (PG) F2alpha to the tissue bath. These drugs and also flufenamic acid and salicin show a similar antagonism of the action of PGF2alpha with isolated rabbit non-pregnant myometrium. The ratio of the inhibitory concentration in vitro to the maximum plasma level after a normal dose in vivo suggests that phenylbutazone and possibly ibuprofen may be capable of inhibiting human uterine contractions in vivo. Patients who were treated with aspirin during induction of abortion using PGF2alpha during the second trimester of pregnancy showed no significant change in the induction-abortion interval compared with patients not taking aspirin.

Effects of a 5-lipoxygenase inhibitor, REV-5901, on leukotriene and histamine release from human lung tissue in-vitro.

REV‐5901, α‐pentyl‐3‐(2‐quinolinylmethoxy)benzene‐methanol, is an arylmethylphenyl ether derivative which inhibits 5‐lipoxygenase activity of leukocytes. Its effects on the release of leukotrienes, induced by antigen and calcium ionophore, from human lung tissue in‐vitro have been examined. At 1 and 10 μM it significantly inhibited the release of leukotrienes induced by both stimuli. At 10 μM it also inhibited antigen‐induced histamine release. These results suggest that REV‐5901 may be useful in clinical disorders such as asthma in which leukotriene release may be involved.

The distribution of a cardiotonic factor, splenitransin, in mammalian tissues

Abstract 1. 1. Splenitransin, the cardiac stimulant substance previously reported in acetone extracts of freeze-dried ox spleen, is shown to be widely distributed in mammalian tissues. 2. 2. It occurs in feline skeletal muscle, heart, liver, kidney, bone marrow and brain, with spleen as the best source. 3. 3. It has been extracted from bovine, feline and human blood and is significantly more concentrated in red cells than plasma in adult species. 4. 4. Its presence in human urine has also been demonstrated.

The inhibition by azatadine of the immunological release of leukotrienes and histamine from human lung fragments

The effects of the H1 antihistamine azatadine on the antigen-induced release of slow reacting substance of anaphylaxis (leukotrienes C4 and D4) and histamine from passively sensitized human lung fragments were determined. Azatadine 0.1-10 microM significantly and dose dependently inhibited the release of leukotrienes from lung by 22-71%. Histamine release was also inhibited by azatadine 10 microM.