The role of central corticotropin-releasing hormone in the anorexic and endocrine effects of the bacterial T cell superantigen, Staphylococcal enterotoxin A.
Bacterial superantigens, such as the staphylococcal enterotoxins, exert a strong capacity for in vivo stimulation of T cell proliferation and cytokine production. Previously, staphylococcal enterotoxin A (SEA) was shown to induce an anorexic effect under novel contextual conditions of testing, and produced an increase in plasma ACTH and corticosterone levels in C57BL/6J mice. In the present study, the role of corticotropin releasing hormone (CRH) in promoting these effects of SEA was addressed via intracerebroventricular (icv) administration of alpha-helical CRH(9-41) ((alpha)hCRH), a non-selective CRH receptor antagonist, and astressin-2B, a selective CRH receptor 2 antagonist. The efficacy of (alpha)hCRH and astressin-2B in blocking anorexic responses to CRH and urocortin under the current conditions of testing was first confirmed. Subsequently, it was found that (alpha)hCRH (20 microg icv), but not astressin-2B (10 and 25 microg icv), significantly attenuated the anorexia induced by SEA. This suggested that central CRH is involved in mediating the anorexia induced by SEA, but potentially through CRH receptor 1. Additional results revealed that plasma ACTH stimulation in response to SEA was not significantly attenuated by either antagonist administered icv. However, the plasma corticosterone elevation showed a modest, but significant, attenuation in SEA challenged mice given (alpha)hCRH. These data suggest a possible influence of central CRH on adrenocorticoid activity subsequent to SEA challenge. More importantly, it appears that central activation of CRH receptors is a consequence of SEA challenge, and this likely contributes to its anorexic effects.
Kaneta
Takehiro
T
Department of Psychology, Biopsychology and Behavioral Neuroscience Program, Rutgers University, 152 Frelinghuysen Road, Piscataway, NJ 08855, USA.
Kusnecov
Alexander W
AW
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D001066:Appetite / Q000187:drug effects / Q000276:immunology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D007369:Interferon Inducers / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology
D004768:Enterotoxins; D006727:Hormone Antagonists; D007369:Interferon Inducers; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C026066:enterotoxin A, Staphylococcal; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D003345:Corticosterone