In vivo modulation of histamine release by autoreceptors and muscarinic acetylcholine receptors in the rat anterior hypothalamus.
The modulation of histamine release by histamine and muscarinic acetylcholine receptors was investigated by using the push-pull technique. The anterior hypothalamic area of the conscious, freely moving rat was superfused through the push-pull cannula with CSF or with CSF containing drugs and the release of endogenous histamine was determined in the superfusate. Hypothalamic superfusion with tetrodotoxin (10 mumol/l) led to a pronounced and sustained decrease in the histamine release rate. Superfusion with compound 48/80 (100 mg/l) was ineffective. Hypothalamic superfusion with the H3 agonist (R)-alpha-methylhistamine inhibited, while superfusion with the H3 antagonist thioperamide enhanced the release of histamine. The release of histamine was inhibited on hypothalamic superfusion with the muscarinic receptor agonists carbachol or oxotremorine. Histamine release was enhanced by atropine, and this release-enhancing effect was abolished by oxotremorine. The selective M1 antagonist pirenzepine (100 mumol/l) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 10 mumol/l), which blocks M1 and M3 receptors, also enhanced the release rate of histamine. On the other hand, 50 and 100 mumol/l methoctramine (M2 receptor antagonist) 10 and 100 mumol/l p-fluoro-hexahydro-siladifenidol (p-F-HHSiD, a M3 receptor antagonist) were ineffective. It is concluded tht histamine released in the hypothalamus originates predominantly from neurons. The release of histamine is modulated by H3 autoreceptors. The histamine release is also modulated by cholinergic neurons which modify histamine release from histaminergic neurons by stimulating M1 muscarinic acetylcholine heteroreceptors probably located on histaminergic neurons.
Prast
H
H
Institut für Pharmakologie und Toxikologie, Universität Innsbruck, Austria.
Fischer
H P
HP
Prast
M
M
Philippu
A
A
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists; D006636:Histamine Release; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013779:Tetrodotoxin
D006633:Histamine Antagonists; D010880:Piperidines; D011976:Receptors, Muscarinic; D013779:Tetrodotoxin; D001285:Atropine; D006632:Histamine; C052075:thioperamide