Brain phospholipase A(2)-arachidonic acid cascade is involved in the activation of central sympatho-adrenomedullary outflow in rats.
The present experiments were designed to explore the role of the brain phospholipase A(2)-arachidonic acid cascade in the activation of central sympatho-adrenomedullary outflow in rats, using melittin (an activator of phospholipase A(2)) and arachidonic acid. Intracerebro-ventricularly administered melittin (2.5, 10, and 25 microg/animal) or arachidonic acid (75, 150, 300 microg/animal) effectively and dose dependently elevated plasma levels of adrenaline and noradrenaline. The elevation of both catecholamines induced by melittin (10 microg/animal) was abolished by centrally administered mepacrine (an inhibitor of phospholipase A(2)), but not by neomycin (an inhibitor of phospholipase C). However, mepacrine had no effect on the increase induced by arachidonic acid (150 microg/animal). Indomethacin (an inhibitor of cyclooxygenase) abolished all responses induced by melittin and arachidonic acid. Furegrelate (an inhibitor of thromboxane A(2) synthase) abolished the elevation of adrenaline induced by melittin and arachidonic acid, but had no effect on the elevation of noradrenaline induced by these compounds. These results suggest that activation of the brain phospholipase A(2)-arachidonic acid cascade facilitates the central sympatho-adrenomedullary outflow in rats. Brain thromboxane A(2) is involved in the activation of central adrenomedullary outflow and an active metabolite of arachidonic acid other than thromboxane A(2) may be involved in activation of the central sympathetic outflow.
Yokotani
K
K
Department of Pharmacology, Kochi Medical School, Nankoku, 783-8505, Kochi, Japan.
Wang
M
M
Murakami
Y
Y
Okada
S
S
Hirata
M
M
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008555:Melitten / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood*; D010741:Phospholipases A / Q000187:drug effects / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D008555:Melitten; D016718:Arachidonic Acid; D010741:Phospholipases A; D011796:Quinacrine; D009638:Norepinephrine; D007213:Indomethacin; D004837:Epinephrine