Sympathetic nerves, but not the adrenal gland, contribute to elevated plasma levels of met-enkephalin in rats with acute cholestatic hepatitis.
Met-enkephalin is known to circulate in human and animal plasma in low levels. However, the source(s) of plasma met-enkephalin have not been completely elucidated. It has been proposed that the adrenal gland, sympathetic nerves, pancreas and the gut might be implicated. Recently, markedly elevated levels of met-enkephalin have been documented in the presence of liver disease. To investigate potential sources of met-enkephalin in liver disease, rats with acute cholestatic hepatitis 24 h after gavage with alpha naphthylisothiocyanate (ANIT) 100 mg/kg were studied. Plasma met-enkephalin levels were determined by radioimmunoassay in plasma samples from normal, adrenalectomized, or chemically sympathectomized animals. In control rats, ANIT treatment resulted in a striking 8.7-fold increase in systemic venous met-enkephalin levels (inferior vena cava) (P < or = 0.0005) and a significant increase in peptidase-derived met-enkephalin levels (determined after trypsin/carboxypeptidase B digestion of plasma samples) (P < or = 0.05). ANIT-treatment also resulted in a 5.6-fold increase in portal vein met-enkephalin levels (P < or = 0.005). Portal vein met-enkephalin levels were only 1.2-fold higher than IVC levels in ANIT-treated rats (P < or = 0.05). Plasma activities of the two main enkephalin degrading enzymes, aminopeptidase and enkephalinase, were similar in control and ANIT-treated rats. Chemical sympathectomy, prior to ANIT treatment, decreased the elevation in inferior vena caval met-enkephalin levels by 35% (P < or = 0.005). Adrenalectomy did not alter ANIT-induced increases in circulating met-enkephalin levels (pNS).(ABSTRACT TRUNCATED AT 250 WORDS)
Swain
M G
MG
Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, MD 20892.
Vergalla
J
J
Bergasa
N V
NV
Jones
E A
EA
D015058:1-Naphthylisothiocyanate; D000311:Adrenal Glands / Q000378:metabolism*; D000315:Adrenalectomy; D000626:Aminopeptidases / Q000097:blood; D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000097:blood* / Q000139:chemically induced; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004744:Enkephalin, Methionine / Q000097:blood*; D006520:Hepatitis, Animal / Q000097:blood* / Q000139:chemically induced; D008297:Male; D015260:Neprilysin / Q000097:blood; D011169:Portal Vein / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000378:metabolism*
D015058:1-Naphthylisothiocyanate; D004744:Enkephalin, Methionine; D000626:Aminopeptidases; D015260:Neprilysin