Brain neuronal/inducible nitric oxide synthases and cyclooxygenase-1 are involved in the bombesin-induced activation of central adrenomedullary outflow in rats

Lianyi Lu, Takahiro Shimizu, Kumiko Nakamura, Kunihiko Yokotani, Lianyi Lu, Takahiro Shimizu, Kumiko Nakamura, Kunihiko Yokotani, Lianyi Lu, Takahiro Shimizu, Kumiko Nakamura, Kunihiko Yokotani

Index: Eur. J. Pharmacol. 590(1-3) , 177-84, (2008)

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Abstract

Brain nitric oxide (NO) is mainly generated by neuronal NO synthase (NOS) and inducible NOS. In various cells, NO has been shown to regulate cyclooxygenase (COX), which is divided into two isoforms, COX-1 and COX-2. We previously reported that bombesin injected into the right lateral ventricle evokes the secretion of noradrenaline and adrenaline from adrenal medulla by brain COX-mediated mechanisms in rats. In the present study, we examined whether NOS is involved and which types of NOS and COX are involved in the bombesin-induced activation of central adrenomedullary outflow using urethane-anesthetized rats. Intracerebroventricularly (i.c.v.) administered bombesin (1 nmol/animal)-induced elevation of plasma noradrenaline and adrenaline was attenuated by pretreatment with N ω -nitro- l-arginine methyl ester (a non-selective NOS inhibitor) (0.37 and 1.11 μmol/animal, i.c.v.). 7-Nitroindazole (a neuronal NOS inhibitor) (0.03 and 0.12 μmol/animal, i.c.v.) attenuated the bombesin-induced elevation of plasma noradrenaline alone, while S-ethylisothiourea (an inducible NOS inhibitor) (2.7 and 27 nmol/animal, i.c.v.) and cycloheximide (an inhibitor of protein synthesis) (0.1 and 0.2 μmol/animal, i.c.v.) only attenuated the bombesin-induced elevation of plasma adrenaline. Furthermore, the bombesin-induced elevation of both catecholamines was attenuated by ketoprofen (a selective COX-1 inhibitor) (1 and 2 μmol/animal, i.c.v.), but not influenced by NS-398 (a selective COX-2 inhibitor) (0.8 and 1.6 μmol/animal, i.c.v.). These results suggest that the brain neuronal NOS/COX-1 and inducible NOS/COX-1 are respectively involved in the bombesin-induced secretion of noradrenaline and adrenaline from the adrenal medulla in rats.