Effects of a selective alpha 2-adrenoceptor antagonist, atipamezole, on hypothalamic histamine and noradrenaline release in vivo.
In vivo microdialysis was used to study the effects of a potent and selective alpha 2-adrenoceptor antagonist, atipamezole, on histamine and noradrenaline release from the medial hypothalamus in anesthetized rats. Local perfusion with atipamezole via the microdialysis probe increased histamine release significantly and dose-dependently. However, the effect of systemic administration of atipamezole (1 mg/kg) was opposite: it significantly decreased histamine release. Local and systemic administration of atipamezole produced an approx. 2-fold increase in noradrenaline release. To study the modulatory effect of noradrenergic neurons on histamine release, noradrenaline synthesis was inhibited with alpha-methyl-p-tyrosine. In the microdialysis experiment, rats that received alpha-methyl-p-tyrosine exhibited no decrease, but rather a slight increase in histamine release in response to systemic atipamezole administration. These results show clearly that atipamezole enhances noradrenaline release in vivo from rat hypothalamus and its effects on histamine release are dependent on the route of drug administration.
Laitinen
K S
KS
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Tuomisto
L
L
MacDonald
E
E
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008781:Methyltyrosines; C050701:atipamezole; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine