Effect of endotoxicosis on plasma and tissue levels of calcitonin gene-related peptide.
This study was designed to investigate the changes in tissue content and plasma concentrations of CGRP, a 37 amino acid vasoactive peptide, in male Sprague Dawley rats injected intravenously with a nonlethal dose of 3 mg/kg E. coli endotoxin. Plasma CGRP concentrations in nonendotoxemic animals, measured by a specific RIA, were initially 30.5 +/- 3.3 pg/ml, and were significantly increased to 63.7 +/- 4.6 pg/ml 2 hr after induction of endotoxemia (P less than 0.001; n = 13). A higher dose of LPS did not further elevate plasma CGRP levels, indicating that the maximal response occurred following a dose of 3 mg/kg LPS. CGRP levels in abdominal aorta, inferior vena cava, stomach, kidney, and left ventricular myocardium (4.11, 8.5, 2.61, 0.69, and 0.25 pmol/g wet weight tissue, respectively) were not changed significantly following the injection of endotoxin. However, in lung and mesenteric artery the levels increased significantly from 1.47 +/- 0.12 and 7.97 +/- 1.32 pmol/g wet weight tissue to 1.96 +/- 0.19 (P less than 0.05, n = 11) and 15.02 +/- 2.3 pmol/g (P less than 0.01; n = 7), respectively. In contrast, CGRP levels in the duodenum were significantly decreased from 11.3 +/- 0.93 pmol/g wet weight tissue to 6.2 +/- 0.68 pmol/g (P less than 0.001; n = 6). The changes in plasma concentration and tissue content of CGRP suggest that splanchnic organs may be the source of the elevated plasma CGRP levels in endotoxemia and that selective organ CGRP levels reflect a role in the pathogenesis of the response to endotoxemia.
Griffin
E C
EC
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
Aiyar
N
N
Slivjak
M J
MJ
Smith
E F
EF
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000378:metabolism*
D004731:Endotoxins; D015740:Calcitonin Gene-Related Peptide