Role of brain prostanoids in glucagon-like peptide-1-induced central activation of sympatho-adrenomedullary outflow in rats.
1. The aim of the present study was to characterize the source of plasma catecholamines induced by centrally administered glucagon-like peptide-1 (GLP-1), with regard to brain prostanoids, in urethane-anaesthetized rats. 2. Glucagon-like peptide-1 and other compounds were administered intracerebroventricularly (i.c.v.) and blood samples were collected via a cannula inserted into the femoral artery. Catecholamines were extracted from plasma with activated alumina and were assayed electrochemically using high-performance liquid chromatography. 3. At 0.3, 1.0 and 3.0 nmol/animal, GLP-1 dose-dependently elevated plasma levels of noradrenaline and adrenaline and the 1.0 nmol GLP-1-induced response was dose-dependently reduced by 5 and 10 nmol/animal exendin (5-39), a selective GLP-1 receptor antagonist. The GLP-1-induced elevation of concentrations of both catecholamines was abolished by 1.2 micromol/animal indomethacin, an inhibitor of cyclo-oxygenase, whereas 1.2 micromol/animal baicalein, a lipoxygenase inhibitor, had no effect. 4. Both furegrelate (1.8 micromol/animal; an inhibitor of thromboxane A(2) synthase) and (+)S-145 (625 nmol/animal; a thromboxane A(2) receptor antagonist) attenuated the GLP-1-induced increases in plasma adrenaline concentrations, but had no effect on the increases in plasma noradrenaline. The GLP-1-induced increase in plasma adrenaline concentrations was abolished by acute bilateral adrenalectomy, but the procedure had no effect on increases in plasma noradrenaline. 5. These results suggest that, in rats, centrally administered GLP-1 induces the secretion of adrenaline from the adrenal medulla by brain thromboxane A(2)-mediated mechanisms, whereas the peptide evokes the release of noradrenaline from sympathetic nerves by brain prostanoids via mechanisms other than those mediated by thromboxane A(2).
Arai
Junichi
J
Department of Pharmacology, Graduate School of Medicine, Kochi University, Nankoku, Kochi, Japan.
Okada
Shoshiro
S
Yamaguchi-Shima
Naoko
N
Shimizu
Takahiro
T
Sasaki
Tsuyoshi
T
Yorimitsu
Mieko
M
Wakiguchi
Hiroshi
H
Yokotani
Kunihiko
K
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011920:Rats, Inbred WF; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D013928:Thromboxane A2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
D002395:Catecholamines; D011453:Prostaglandins; D013928:Thromboxane A2; D052216:Glucagon-Like Peptide 1