Perfusion of the hypothalamic paraventricular nucleus with N-methyl-D-aspartate produces thromboxane A2 and centrally activates adrenomedullary outflow in rats.
We applied a microdialysis technique for the measurement of hypothalamic thromboxane B2, a stable metabolite of thromboxane A2, in urethane-anesthetized rats. Perfusion with N-methyl-D-aspartate (1.5 and 2.5mM) of the paraventricular nucleus by microdialysis probe concentration-dependently elevated the levels of thromboxane B2 in this region and plasma levels of catecholamines. The elevation of adrenaline was much more marked than that of noradrenaline. Pretreatment with dizocilpine maleate (0.1 mM), a non-competitive antagonist of N-methyl-D-aspartate receptors, of the paraventricular nucleus by microdialysis probe attenuated the N-methyl-D-aspartate (1.5 mM)-induced elevations of both thromboxane B2 and plasma catecholamines. Intracerebroventricular administration of furegrelate (250 microg/animal), a thromboxane A2 synthase inhibitor, also abolished the responses evoked by N-methyl-D-aspartate. These results indicate that N-methyl-D-aspartate applied into the paraventricular nucleus produces thromboxane A2 in this region and elevates plasma levels of catecholamines, especially adrenaline. Thromboxane A2 produced in this hypothalamic nucleus is probably involved in the N-methyl-D-aspartate-induced central adrenomedullary outflow.
Okada
S
S
Department of Pharmacology, Kochi Medical School, Nankoku, Kochi, Japan. Okadas@med.kochi-ms.ac.jp
Murakami
Y
Y
Nishihara
M
M
Yokotani
K
K
Osumi
Y
Y
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001572:Benzofurans; D002395:Catecholamines; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D013929:Thromboxane B2; D013928:Thromboxane A2; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D013930:Thromboxane-A Synthase; C039936:furegrelate