Involvement of histaminergic neurons in the stress-induced release of pro-opiomelanocortin-derived peptides in rats.
Histamine, which acts as a neurotransmitter, stimulates the release of the pro-opiomelanocortin derived peptides ACTH, beta-lipotropin, and beta-endorphin. Since stress affects the hypothalamic turn-over of neuronal histamine, we investigated the role of histaminergic neurons in the mediation of the stress-induced release of ACTH and beta-endorphin immunoreactivity in male rats. In control animals histamine receptor antagonists had no effect on the release of ACTH or beta-endorphin immunoreactivity. Restraint and ether stress increased plasma ACTH 3- and 2-fold, respectively. The responses were almost prevented by intracerebroventricular or intra-arterial infusion of the H2-receptor antagonists cimetidine and ranitidine. Infused intracerebroventricularly the H1-receptor antagonist mepyramine inhibited the ACTH response to restraint by 45% (P less than 0.01), but had no effect on the response to ether. Infused intra-arterially the H1-receptor antagonists mepyramine or SKF-93944 had no effect. Restraint and ether stress increased plasma beta-endorphin immunoreactivity 6- and 5-fold, respectively. Sephadex G-50 gel chromatography of plasma showed that the beta-endorphin immunoreactivity in stressed rats co-eluted with beta-lipotropin and beta-endorphin, whereas the immunoreactivity in control animals co-eluted almost exclusively with beta-endorphin. The H2-receptor antagonists cimetidine and ranitidine infused intracerebroventricularly inhibited the responses of beta-endorphin immunoreactivity to restraint and ether stress by 90 and 70%, respectively, whereas intra-arterial infusion of these antagonists inhibited the responses by only 50 and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Knigge
U
U
Institute of Medical Physiology C, Panum Institute, University of Copenhagen, Denmark.
Matzen
S
S
Bach
F W
FW
Bang
P
P
Warberg
J
J
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002850:Chromatography, Gel; D002927:Cimetidine / Q000008:administration & dosage; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D008297:Male; D011738:Pyrilamine / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000097:blood / Q000503:physiopathology*; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*; D008083:beta-Lipotropin / Q000097:blood / Q000378:metabolism*
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011744:Pyrimidinones; D001615:beta-Endorphin; D002927:Cimetidine; D000324:Adrenocorticotropic Hormone; D008083:beta-Lipotropin; C049054:temelastine; D011738:Pyrilamine