Calcitonin gene-related peptide release in endotoxicosis may be mediated by prostaglandins.
Three cyclo-oxygenase inhibitors (ibuprofen, indomethacin, and high dose aspirin) and two inhibitors of thromboxane biosynthesis (imidazole and low dose aspirin) were used to evaluate the role of prostaglandins and thromboxane in the release of calcitonin gene-related peptide (CGRP) during endotoxicosis. Endotoxin (lipopolysaccharide B from Salmonella Enteritidis, 5 mg/kg, intravenously) was administered to rats lightly anesthetized with ether during injection. After 3 h, endotoxin significantly elevated plasma CGRP levels by 3-fold. Ibuprofen (50 mg/kg, subcutaneously), indomethacin (10 mg/kg, subcutaneously) and high dose aspirin (100 mg/kg, intraperitoneally (i.p.)), but not imidazole (30 mg/kg, i.p.) or low dose aspirin (15 mg/kg, i.p.), significantly blocked endotoxin-induced CGRP elevations, suggesting that a prostaglandin, but not thromboxane, served as a mediator of CGRP release during endotoxicosis. Because endotoxin-induced production of prostaglandins is greatly diminished in endotoxin-tolerant rats (following multiple exposures to low dose endotoxin), we tested whether endotoxin-induced CGRP release also becomes diminished in tolerant rats. Accumulation of plasma CGRP was greatly diminished in endotoxin-tolerant rats exposed to endotoxin (5 mg/kg, intravenously), consistent with a mediator role for prostaglandins in the CGRP release during endotoxicosis.
Institute of Vascular Medicine, Third Clinical College Beijing Medical University, People's Republic of China.
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Wang
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Han
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Jones
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Yang
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Fiscus
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004361:Drug Tolerance; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D007773:Lactates / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D013931:Thromboxanes / Q000096:biosynthesis / Q000502:physiology
D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D007773:Lactates; D008070:Lipopolysaccharides; D011453:Prostaglandins; D013931:Thromboxanes; C036757:lipopolysaccharide B; C029899:imidazole; D015740:Calcitonin Gene-Related Peptide; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin