Prostaglandin synthetase activity from human rheumatoid synovial microsomes. Effect of 'aspirin-like' drug therapy.

Crook, David; Collins, A. J.; Bacon, P. A.; Chan, Rena

doi:10.1136/ard.35.4.327

Cited by 57 publications

(18 citation statements)

References 12 publications

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“…5 also shows that these changes in Isc reflect changes in Cl transport. As is the case for other secretory stimuli in rabbit ileum (26), the changes in net Cl flux were about twice as large as the changes in Isc. This is due to the fact that secretory stimuli also inhibit net Na absorption, thereby diminishing the overall change in Isc (2, 6).…”

Section: Methodsmentioning

confidence: 75%

Bradykinin-stimulated electrolyte secretion in rabbit and guinea pig intestine. Involvement of arachidonic acid metabolites.

Musch¹,

Kachur²,

Miller³

et al. 1983

J. Clin. Invest.

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A B S T R A C T Bradykinin (BK) increases short-circuit current (Isc) when added to the serosal side of rabbit or guinea pig ileum or rabbit colon. Significant effects on Isc are seen at concentrations as low as 10-' M. Anion substitution experiments and unidirectional 36C flux measurements indicate that this effect of BK on Isc is due to Cl secretion. The effect of BK on Isc can be partially blocked (60-70% inhibition) by cyclooxygenase inhibitors (indomethacin and/or naproxen) and completely blocked by the phospholipase inhibitor, mepacrine. The combined cyclooxygenase/lipoxygenase inhibitors BW 755 and eicosa-5,8,11,14-tetraynoic acid (ETYA) also completely block the effect of BK on Isc but the slow-reacting substance of anaphylaxis (SRS-A) antagonist FPL 55712 has no effect. None 5 January 1983. this effect can be blocked by prior addition of either indomethacin or mepacrine. These effects of BK are similar to those of exogenously added arachidonic acid (AA). AA also stimulates Cl secretion and increases PGE2 synthesis and its effect on Isc can be inhibited by prior desensitization to PGE2 or by prior addition of indomethacin. The above results indicate that BK stimulates active Cl secretion in both small and large intestine and suggest that this effect is due to the intracellular release of AA. Although the prostaglandins appear to be the major products of AA metabolism contributing to the secretory response, lipoxygenase products may also play a role.

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Section: Methodsmentioning

confidence: 75%

Bradykinin-stimulated electrolyte secretion in rabbit and guinea pig intestine. Involvement of arachidonic acid metabolites.

Musch¹,

Kachur²,

Miller³

et al. 1983

J. Clin. Invest.

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“…Of greater interest is which of these actions of the conventional drugs is more relevant to their clinical antirheumatic effects. Recent work [17] showing that small analgesic doses of aspirin, which are not capable of exerting anti-inflammatory effects in human rheumatoid arthritis, may totally inhibit prosta- glandin biosynthesis in synovial tissue from patients with the disease suggests that it is the effect on leucocyte migration [8] which is the more important.…”

Section: Resultsmentioning

confidence: 97%

Prostaglandins and leucocyte migration in inflammatory reactions

et al. 1977

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“…Similar to the endotoxin model, ewes primed with ibuprofen or indomethacin and then challenged with TCA-878 also failed to experience pulmonary hypertension or decreases in FAP or arterial Poz. Ibuprofen and indomethacin reduce PG production by inhibiting PG synthetase (4,5). The prevention of pulmonary hypertension and the other vascular changes induced by TCA-878 suggest that PG may play an important role in their genesis.…”

Section: Discussionmentioning

confidence: 99%

Studies of Short-Term Pulmonary and Peripheral Vascular Responses Induced in Oophorectomized Sheep by the Infusion of a Group B Streptococcal Extract

et al. 1984

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SummaryShort-term (0-30 min) pulmonary and systemic vascular responses of oophorectomized ewes infused intravenously with a trichloroacetic acid (TCA) extract of a type I11 (strain 878) group B streptococci?s (GBS) were studied. TCA-878 extract induced significant pulmonary hypertension, reduction in femoral artery pressure and reduced femoral artery Po2. These responses were similar to those observed after the infusion of sublethal doses of E. coli endotoxin and could be prevented by priming the animal with ibuprofen or indomethacin. Ewes rechallenged 48 h after their initial dose of TCA-878 extract experienced pulmonary arterial pressure significantly higher than those induced by the first infusion. Similar augmented responses were not seen after rechallenge with endotoxin. Larger doses of TCA-878 extract resulted in increasingly higher pulmonary arterial pressure. We conclude that the venous infusion of TCA extracts of GBS-878 induces significant pulmonary hypertension in sheep and that this response may be mediated by prostaglandins. The vasoactive substance extracted from these streptococci could play a role in promoting the vascular instability experienced by the human neonate with early onset GBS disease. Abbreviations FAP, femoral artery pressure GBS, group B streptococci PAP, pulmonary artery pressure PG, prostaglandins SDS-PAGE, sodium dodecyl sulfate-polyacrylamid gel electrophoresis TCA, trichloroacetic acid GBS are common causes of serious infections in the human neonate (1,8). Though the clinical syndromes caused by GBS are well described, little is known of how these organisms induce the attendent physiologic abnormalities. Recently, Hellerqvist, et al. (7) and Rojas et al. (13) reported the isolation of a carbohydrate "exotoxin" from the culture media in which type 111 GBS had been grown. Intravenous infusion of this material was found to induce pulmonary hypertension, fever, and increase pulmonary lymphatic flow in adult sheep. At the time of the Hellerqvist and Rojas reports (7, 13), we were preparing TCA extracts of washed, whole GBS for utilization in studies of GBS antigens. One person in our group (W.F.O.) was utilizing the oophorectomized adult ewe model of Cefalo et al. (2, 3, 11) to examine the early phase of vascular responses in sheep after the venous infusion of E. coli endotoxin. Noting some striking similarities in PAP responses induced by the Rojas' "exotoxin" and E. coli endotoxin, we infused sterile TCA extract of whole GBS (type 111, 878) into an oophorectomized ewe. The infusion resulted in a prompt and impressive rise in PAP, a reduction in FAP, and a drop in femoral artery Po2. Once our studies had excluded endotoxin contamination of whole organism extracts (TCA-878) and produced a predictable vascular response in the available ewe model, we devised studies: 1) to compare the vascular responses induced by TCA-878 extract with those induced by E. coli endotoxin; 2 ) to examine responses to increasing concentrations of TCA-878; 3) to determine whether, as reported with endotoxi...

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Prostaglandin synthetase activity from human rheumatoid synovial microsomes. Effect of 'aspirin-like' drug therapy.

Cited by 57 publications

References 12 publications

Bradykinin-stimulated electrolyte secretion in rabbit and guinea pig intestine. Involvement of arachidonic acid metabolites.

Bradykinin-stimulated electrolyte secretion in rabbit and guinea pig intestine. Involvement of arachidonic acid metabolites.

Prostaglandins and leucocyte migration in inflammatory reactions

Studies of Short-Term Pulmonary and Peripheral Vascular Responses Induced in Oophorectomized Sheep by the Infusion of a Group B Streptococcal Extract

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