Histamine contraction of isolated human airway muscle preparations: role of prostaglandins.

Histamine concentration-effect curves were obtained using either an individual or cumulative dosing method. The maximal response to histamine in bronchial preparations using the individual dosing protocol was 0.25 +/- 0.03 g/mm2 and similar results were obtained using the cumulative method (0.24 +/- 0.03 g/mm2). The sensitivity (pD2 value) of isolated human bronchial muscle preparations was comparable for both the individual and cumulative methods (5.71 and 5.16, respectively). Prostaglandin (PG) E2 and PGF2 alpha contracted isolated human bronchial muscle preparations and the pD2 values were 5.64 and 5.59, respectively. PGE2 did not relax bronchial muscle preparations contracted with histamine (50 microM). At high concentrations prostacyclin (3 microM) relaxed histamine-contracted bronchial tissues but this effect was quite variable. Indomethacin (1.7 microM) did not affect basal tone in bronchial tissues. Isolated human bronchial preparations which were contracted maximally with histamine always released measurable quantities of PGs. In some experiments the rat stomach strip was used to detect the presence of these substances before and subsequent to the indomethacin (1.7 microM) treatment. The use of radioimmunoassay for PGE2 and PGF2 alpha confirmed these bioassay results. In a large number of experiments (18 preparations from 9 individual lung samples) the baseline production of PGs was PGE2, 22.9 +/- 2.8 pg/mg of tissue and PGF2 alpha, 11.9 +/- 2.5 pg/mg of tissue. Subsequent to histamine stimulation the quantities of PGs released were PGE2, 72.4 +/- 7.6 pg/mg of tissue and PGF2 alpha, 40.9 +/- 7.3 pg/mg of tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

[Synthesis of paf-acether by E. coli K12]. / Synthèse du paf-acéther par E. coli K12.

Paf-acether (platelet-activating factor) is one of the most potent mediator of inflammation released from and acting on most cells that participate in inflammatory diseases. Its molecular structure is 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine. Two metabolic steps are involved in its biosynthesis: the action of a phospholipase A2 on choline-containing membrane alkyl-ether lipids results in the production of lyso paf-acether and acetylation of the lyso compound by an acetyltransferase yields the biologically active molecule. Membrane alkyl-ether lipids can therefore be considered as potential precursors of paf-acether and their composition has been studied in various cell types. In this work, we investigated the presence of paf-acether in E. coli. Our results showed that paf-acether can be obtained from E. coli K12 under a variety of bacterial growth conditions. Paf-acether from E. coli exhibited the same physicochemical and biological characteristics as synthetic paf-acether and that from eucaryotic cells. Therefore, it appears that E. coli itself has the ability of producing paf-acether, a result that could be of some importance with respect to the pathogenesis of Enterobacteria and the use of E. coli in the recombinant DNA technology.

Response and sensitivity of isolated human pulmonary muscle preparations to pharmacological agents.

The responsiveness (grams per millimeter squared) and sensitivity (pD2 value) of various agonists were examined in isolated stored human bronchial and pulmonary arterial and venous preparations. In isolated bronchial muscles, large preparations (internal diameter about 6 mm) were less responsive (grams per millimeter squared) to contractile agents than smaller preparations (internal diameter approximately 2 mm). Noncumulative concentration-effect curves were produced in bronchial preparations using histamine, acetylcholine, carbachol and barium chloride. Histamine contracted both bronchial and vascular preparations whereas 5-hydroxytryptamine contracted only vascular tissues. The latter effect was always blocked by either methysergide or ketanserin. 5-hydroxytryptamine relaxed bronchial tissues that were contracted with either histamine, acetylcholine or prostaglandin E2. This relaxation was not antagonized by methysergide, ketanserin, propranolol or indomethacin. Dimaprit and 4-methyl histamine were without effect in isolated contracted bronchial preparations. Vasoactive intestinal peptide, Substance P and platelet-activating factor when added to preparations at resting tone failed to induce a contraction. These agents did not relax histamine-contracted isolated human pulmonary muscle preparations. Anti-immunoglobulin E antibody sometimes contracted isolated human bronchial muscle but not pulmonary vascular preparations. However, these data were difficult to assess because of the variations observed. Anti-immunoglobulin G antibody was inactive. Noradrenaline did not elicit a physiological response in isolated bronchial muscle preparations at concentrations which always induced a contraction in the pulmonary vascular preparations. In the presence of propranolol, noradrenaline neither contracted nor relaxed isolated human bronchial preparations. We also determined the sensitivity of isolated bronchial muscle preparations to isoproterenol, salbutamol and theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Chlamydia psittaci experimental abortion in goats.

To study abortive chlamydiosis in goats, 11 pregnant goats were inoculated intradermally at the 3rd month of pregnancy with 2 X 10(7) or 2 X 10(6) plaque-forming units of a strain of Chlamydia psittaci isolated from naturally occurring abortions in goats. The 11 inoculated does aborted 24 to 56 days after they were inoculated and shed Chlamydia. This shedding began at least 9 days before abortion (1 goat) and persisted 12 days after abortion (1 goat). Retained placenta or metritis were observed in 4 of the goats.

The actions of Paf-acether (platelet-activating factor) on guinea-pig isolated heart preparations.

Paf-acether (platelet-activating factor) is a phospholipid capable of stimulating platelets to release their granular contents and cause platelet aggregation. When Paf-acether was administered to isolated heart preparations from normal guinea-pigs there was a significant concentration-dependent reduction in coronary flow and contractile force. The high concentration of Paf-acether was equally effective in reducing these cardiac parameters in the presence of atropine. The non-acetylated Paf-acether analogue, 2-lyso Paf-acether, the enantiomer, and a closely related phospholipid 1, alpha-lysophosphatidylcholine palmitoyl, did not affect coronary flow and contractile force, indicating the specificity of Paf-acether. These data demonstrate a potent effect of Paf-acether on cardiac function. Whether or not these effects are direct or mediated through generation of endogenous mediators remains to be established.

[Release of platelet activating factor (P.A.F.-acether) by isolated perfused rat kidney]. / Libération du facteur activant les plaquettes (P.A.F.-acéther) par perfusion du rein isolé de rat.

Platelet-activating factor (a 1-0-alkyl-2-acetyl glyceryl-3-phosphorylcholine, P.A.F.-acether) causes the aggregation of platelets from various Mammalian species and the release of their granule content. P.A.F.-acether activity has been recovered in vitro from perfused isolated Rat kidneys, stimulated by the ionophore A 23187. The maximum release was reached 10 min. after addition of the ionophore. P.A.F.-acether from kidney exhibited the same physico-chemical and biological characteristics as P.A.F.-acether from leucocytes. These data demonstrate that the kidney secretes a mediator of immediate hypersensitivity (P.A.F.-acether) in the veinous vasculature. Therefore the kidney itself has the ability of inducing intravascular platelet aggregation with subsequent local increase in vasopermeability.

[Semi-synthesis and proposed structure of platelet-activating factor (P.A.F.): PAF-acether an alkyl ether analog of lysophosphatidylcholine]. / Semi-synthèse et structure proposée du facteur activant les plaquettes (P.A.F.): PAF-acether, un alkyl ether analogue de la lysophosphatidylcholine.

We have studied the molecular structure of platelet-activating factor" (P.A.F.), a mediator of inflammation obtained from blood leukocytes, macrophages, and platelets themselves. We have semi-synthetized a substance that possesses all the known physicochemical and biological characteristics of P.A.F. from hog leukocytes. This was performed by successive methylation, hydrogenation, and acetylation of lysophosphatidylethanolamine plasmalogen. We therefore propose the following structure for P.A.F.: 1-0-alkyl-2-acetyl-glyceryl-3-phosphorylcholine. This molecular structure is not yet described among the numerous substances capable of inducing platelet aggregation and release.