Interleukin-1 (IL-1) stimulates the release of corticotropin-releasing factor (CRF) from superfused rat hypothalamo-neurohypophyseal complexes (HNC) independently of the histaminergic mechanism.
We demonstrated previously that interleukin-1 (IL-1) (recombinant human IL-1 alpha and -1 beta) stimulated the release of corticotropin-releasing factor (CRF) from the superfused rat hypothalamo-neurohypophyseal complex (HNC), independently of the cholinergic system. In the present study we studied the effects of IL-1 on the release of CRF not only from the HNC but also from the isolated hypothalamus of rats in a superfusion system to define the origin of measured CRF and the site of IL-1 action. We also studied the possible involvement of the histaminergic system in the mediation of the stimulation by IL-1. An increase in CRF was elicited from the HNC and the isolated hypothalamus in a dose-dependent manner by human recombinant IL-1 beta in concentrations of 0.1-10 nM with similar time courses. Histamine in concentrations of 1-100 nM also elicited qualitatively similar increases of CRF from these two types of explants. The increases in CRF release from the HNC induced by 10 nM of histamine were completely suppressed in the combined presence of pyrilamine (10 microM) and cimetidine (10 microM), an H1 and an H2 receptor antagonist, respectively. On the other hand, the increase in CRF release induced by 10 nM IL-1 beta was not affected by the combination of these two antagonists. These results indicate that IL-1 stimulates CRF release from the median eminence through an action on the hypothalamus, and that the stimulatory effect of IL-1 is probably independent of the histaminergic system.
Ohgo
S
S
Department of Medicine, Miyazaki Medical College, Japan.
Nakatsuru
K
K
Ishikawa
E
E
Matsukura
S
S
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D011738:Pyrilamine / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D006633:Histamine Antagonists; D007375:Interleukin-1; D002927:Cimetidine; D006632:Histamine; D003346:Corticotropin-Releasing Hormone; D011738:Pyrilamine