Neuroendocrinology
Corticotropins and Neuroimmune Interactions
Systemically Administered Histamine H1 and H2 Receptor Antagonists Do Not Block the ACTH Response to Bacterial Lipopolysaccharide and lnterleukin-1Perlstein R.S.a · Mehta N.R.a · Mougey E.H.c · Neta R.a · Whitnall M.H.bDepartments of aExperimental Hematology and bPhysiology, Armed Forces Radiobiology, Research Institute, Bethesda, Md., cNeuroendocrinology and Neurochemistry Branch, Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, D.C., USA Key Words
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Article / Publication Details
Received: February 03, 1994
Accepted: May 24, 1994
Published online: April 09, 2008
Issue release date: 1994
Number of Print Pages: 8
Number of Figures: 0
Number of Tables: 0
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
Abstract
The administration of lipopolysaccharide (LPS) results in the activation of the hypothalamic-pituitary-adrenal axis (HPAA). We recently reported that the participation and interaction of LPS-induced proinflammatory cytokines were obligatory for the stimulation of adrenocorticotropic hormone (ACTH) release by LPS. LPS and LPS-derived cytokines also stimulate the release of histamine (HA). HA is a known hypothalamic neurotransmitter and activates the HPAA. Therefore, to elucidate the role of HA in LPS- and cytokine-induced ACTH release, we evaluated the effects of several HA H1 and H2 receptor antagonists on the ACTH response to LPS, recombinant human interleukin-lα (rhIL-lα) and HA in mice. Although all 3 of the Hi receptor antagonists administered (mepyramine (MEP), diphenhydramine (DPH) or promethazine (PMZ)) were able to block the 10-min ACTH response to HA, only PMZ (a less selective Hl· receptor antagonist than MEP) was able to reduce the LPS- or rhIL-lα-induced ACTH responses. Ranitidine, a powerful and selective H2 receptor antagonist, had little effect on the LPS- and rhIL· lα-induced ACTH responses, while metiamide (MET), a much less potent first-generation H2 receptor antagonist, substantially diminished ACTH release. The greater effectiveness of PMZ, in contrast to MEP or DPH, probably relates to the ability of phenothiazine derivatives to inhibit non-HA-depen-dent pathways involved in the stimulation of the HPAA by cytokines; the same may be true of MET. Our results suggest that, in contrast to the essential role of HA in the activation of the HPAA by noninflammatory stressors, the stimulation of ACTH release by LPS and rhIL-lα is not as dependent on the participation of either the H1 or the H2 receptor.
© 1994 S. Karger AG, Basel
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Article / Publication Details
Received: February 03, 1994
Accepted: May 24, 1994
Published online: April 09, 2008
Issue release date: 1994
Number of Print Pages: 8
Number of Figures: 0
Number of Tables: 0
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
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