Type I interleukin-1 receptors in the mouse brain-endocrine-immune axis labelled with [125I]recombinant human interleukin-1 receptor antagonist.
Iodine-125-labelled recombinant human interleukin-1 (IL-1) receptor antagonist ([125I]IL-1ra) was utilized to further determine the characteristics of IL-1 receptors in the brain-endocrine-immune axis. The binding of [125I]IL-1ra in homogenates of mouse hippocampus, spleen and testis was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity (KD, 20-30 pM). In competition studies, IL-1ra, recombinant human IL-1 alpha, IL-1 beta and a weak IL-1 beta analog inhibited [125I]IL-1ra binding to mouse tissues in parallel with their biological activities. In autoradiographic studies, [125I]IL-1ra and [125I]IL-1 alpha binding showed comparable distribution patterns with highest densities of binding sites present in the dentate gyrus of the hippocampus, choroid plexus, anterior pituitary, marginal zones and red pulp regions of the spleen, epididymis and interstitial area of the testis. The binding characteristics and distribution of [125I]IL-1ra are comparable to those of previously characterized Type I IL-1 receptors. These data provide further support for a role for IL-1 in coordinating brain-endocrine-immune responses to physiological and pharmacological stimuli.
Takao
T
T
Central Nervous System Diseases Research, DuPont Merck Pharmaceutical Company, Wilmington, DE 19880-0400.
Culp
S G
SG
Newton
R C
RC
De Souza
E B
EB
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013154:Spleen / Q000378:metabolism*; D013379:Substrate Specificity; D013737:Testis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003346:Corticotropin-Releasing Hormone