Rapid protein synthesis and turnover is involved in interleukin-1-induced relaxation of the rabbit isolated mesenteric artery. Analysis of the arachidonate cascade.
The rabbit isolated superior mesenteric artery, when precontracted with phenylephrine, relaxes in a sustained manner in less than 30 min when exposed to recombinant interleukin-1 (IL-1), and this is a prostaglandin (PG)-dependent, endothelium- and 5-lipoxygenase-independent process. We have studied the dependency of IL-1-induced relaxation on protein synthesis and trafficking using isolated rings of rabbit mesenteric arteries. Three chemically unrelated protein synthesis inhibitors (PSIs) (cycloheximide, anisomycin and puromycin) completely prevented the response to IL-1. Moreover, the PSIs reversed IL-1-induced relaxations within 15 to 30 min of application. The amplitude and/or the duration of the relaxation induced by arachidonic acid and iloprost (a PGI2 mimetic) were partially inhibited by cycloheximide treatment, but not those induced by nitroglycerin or by cromakalim. However, tissues initially relaxed by IL-1 and then recontracted by a PSI are still able to relax when challenged with either arachidonic acid or iloprost, suggesting that cyclooxygenase is not depleted and that the responsiveness to PGs is intact under these conditions. Manoalide, thioether amide glycerophosphocholine (type II phospholipase A2 inhibitors) or brefeldin A (an inhibitor of intracellular protein trafficking) did not inhibit IL-1-induced relaxation. The data suggest the involvement of newly synthesized protein(s) with a very rapid turnover in the vascular response to IL-1. PSIs probably act at several levels to inhibit the relaxant response to IL-1, but depletion of tissue cyclooxygenase does not appear to be the limiting mechanism for the PSI effect on IL-1-induced relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)
Petitclerc
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Centre de recherche de l'Hôtel-Dieu de Québec, Canada.
Poubelle
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Marceau
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D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011453:Prostaglandins / Q000494:pharmacology; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D007375:Interleukin-1; D011453:Prostaglandins; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D016718:Arachidonic Acid