Degradation of porstaglandin F2alpha in the human pulmonary circulation.

Acute inflammation was induced by intraperitoneal injection of zymosan (yeast cell walls) in the rabbit. Peritoneal inflammation was monitored by the local accumulation of intravenously‐injected Evans blue dye (which binds to plasma albumin) and of polymorphonuclear leukocytes (PMNLs). The zymosan‐induced exudate fluid contained a microvascular permeability‐increasing factor or factors which, unlike histamine and bradykinin, had a long duration of action when tested in rabbit skin and was dependent on circulating PMNLs. Using radioimmunossay, high levels of rabbit C5a, or C5a des Arg, were detected in the exudate fluid and accounted for much of the permeability‐increasing activity, as judged by skin bioassay after separation on Sephadex G‐100. The vasodilator prostaglandin, prostaglandin I2 (PGI2), was generated in the inflammatory reaction, as judged by the presence of high levels of 6‐oxo‐PGF1α detected in the exudate by radioimmunossay. However, in contrast to observations in rabbit skin, inhibition of prostaglandin generation had a relatively small effect on peritoneal oedema formation. C5a and C5a des Arg increase microvascular permeability by a PMNL‐dependent mechanism in the rabbit. However, in response to zymosan, protein leakage was detected considerably earlier than PMNL accumulation. A hypothesis to account for this difference is proposed.

Section: Radioimmunoassayfor Prostaglandinsmentioning

confidence: 99%

Kinetics of the generation and action of chemical mediators in zymosan‐induced inflammation of the rabbit peritoneal cavity

Forrest

Jose

Williams

1986

“…These samples were partially purified using Sep-Pak C18 cartridges and then assayed for the presence of immunoreactive PGE2 and immunoreactive 6-keto PGF1., the stable metabolite of PGI2, according to the method of Jose et al (1976). In these experiments four organ baths were set up each containing a zig-zag preparation obtained from the same guinea-pig trachea.…”

Section: Radioimmunoassaymentioning

confidence: 99%

The role of the epithelium in modulating the responses of guinea‐pig trachea induced by bradykinin in vitro

Bramley

Samhoun

Piper

1990

The effect of removing the epithelium on the responses of the guinea‐pig isolated trachea (GPT) to bradykinin (BK) and prostaglandin E2 (PGE2) was investigated. BK (3 pmol–10 nmol) induced dose‐related relaxations of the intact (with epithelium), and contracted the rubbed (without epithelium) preparation of GPT. Similar responses were also obtained with PGE2 (0.3–3.0 nmol). Indomethacin (1.4 μm) modified the BK‐induced response of intact GPT, from a relaxation to a contraction, but inhibited the BK‐induced contraction of the rubbed GPT. There was a significant increase in PGE2 release from the intact GPT following stimulation with BK. Removal of the epithelium from the GPT significantly reduced both basal and BK‐induced generation of PGE2. The induction of tone in the rubbed GPT by addition of acetylcholine (ACh) caused BK and PGE2 (0.3 nmol–3 nmol) to produce relaxations of the tissue. Salbutamol (10−8 m‐10−6 m) reduced the relaxations induced by BK on intact GPT, in a concentration‐dependent manner. These results suggest that both tone and an epithelial‐dependent cyclo‐oxygenase mechanism are important in modulating BK‐induced responses of GPT.

“…Radioimmunoassay for cyclo-oxygenase products was performed according to the method of Jose et al (1976). The cross-reactivities for the antisera for 6-keto-PGFIc, and thromboxane B2 (TXB2) have been previously reported (Watts et al, 1982).…”

Section: Radioimmunoassaymentioning

confidence: 99%

Coronary vasoconstriction in the rat, isolated perfused heart induced by platelet‐activating factor is mediated by leukotriene C₄

Piper

Stewart

1986

1 Platelet-activating factor (Paf, 0.04-4.50 nmol) dose-dependently induced coronary vasoconstriction and decreased cardiac contractility in rat, isolated perfused hearts and concomitantly released leukotriene-like bioactivity into the cardiac effluent.2 Platelet-activating factor (0.9 nmol) induced an increase in 6-keto-prostaglandin Fl (6-keto-PGFI.), PGF2., PGE2 and thromboxane B2 (TXB2) measured by radioimmunoassay (RIA) of cardiac effluents following partial purification using C18 Sep-Paks. 3 The leukotriene-like bioactivity released by Paf was identified as leukotriene C4 (LTC4) using a combination of isolation on reverse phase-h.p.l.c. (r.p.h.p.l.c.) and quantitation by RIA. In addition, LTB4 was also identified by r.p.h.p.l.c. and the levels, determined by RIA, were within the range having biological activity. 4 The release ofcyclo-oxygenase products by Pafwas prevented by indomethacin (2.8 pM), markedly attenuated by diethylcarbamazine (7.7mM) but unaffected by FPL 55712 (1.9 pM)-pretreatment. Furthermore, LTC4 (50 pmol) did not increase the release of the cyclo-oxygenase products measured. 5 The release of LTB4 and LTC4 appeared to be unaffected by indomethacin pretreatment whereas diethylcarbamazine-pretreatment markedly inhibited release. 6 The coronary vasoconstriction induced by Paf (0.9 nmol) was attenuated by pretreatment with indomethacin or diethylcarbamazine, whereas FPL 55712 caused a marked inhibition of the response. In contrast, the decrease in cardiac contractility was prevented by indomethacin or diethylcarbamazine and unaffected by FPL 55712 pretreatment. 7 It is concluded that LTC4 may be largely responsible for the coronary vasoconstriction induced by Paf with cyclo-oxygenase products having a possible modulatory role whereas the latter appear to be involved in the Paf-induced decrease in cardiac contractility.