Specific up-regulation of CRH or AVP secretion by acetylcholine or lipopolysaccharide in inflammatory susceptible Lewis rat fetal hypothalamic cells.
Lewis (LEW/N) rats, compared to Fischer (F344/N) rats, are susceptible to inflammatory/autoimmune diseases, in part, as a result of their blunted hypothalamic-pituitary-adrenal (HPA) axis responses. We examined regulation of LEW/N and F344/N fetal hypothalamic cell secretion of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), two major HPA axis mediators, by inflammatory and neurotransmitter stimuli. Interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and protein kinase A (PKA) and protein kinase C (PKC) activators did not affect LEW/N basal secretion. Compared to F344/N, LEW/N cells were hyporesponsive to lipopolysaccharide (LPS), serotonin (5-HT), and acetylcholine chloride (ACh). However, LPS-induced AVP release and ACh-evoked CRH secretion in LEW/N were comparable with those of F344/N. Our findings suggest that the blunted LEW/N neuropeptide response was more likely related to components of second messenger systems, rather than to any one specific stimulus.
Wei
Rongtai
R
Integrative Neural Immune Program, NIMH, NIH, 36 Convent Drive, Room 1A23, Bethesda, MD 20892-4020, USA.
Phillips
Terry M
TM
Sternberg
Esther M
EM
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012701:Serotonin / Q000494:pharmacology; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D001127:Arginine Vasopressin; D005576:Colforsin; D012701:Serotonin; D003346:Corticotropin-Releasing Hormone; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate