European Journal of Pharmacology 2005-05-09

Brain phospholipase C/diacylglycerol lipase are involved in bombesin BB2 receptor-mediated activation of sympatho-adrenomedullary outflow in rats.

Takahiro Shimizu, Shoshiro Okada, Naoko Yamaguchi, Junichi Arai, Hiroshi Wakiguchi, Kunihiko Yokotani

Index: Eur. J. Pharmacol. 514(2-3) , 151-8, (2005)

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Abstract

Bombesin receptors are mainly divided into two subtypes: BB1 receptor (neuromedin B-preferring receptor) and BB2 receptor [gastrin-releasing peptide (GRP)-preferring receptor]. Previously, we reported that intracerebroventricularly (i.c.v.) administered bombesin elevates plasma noradrenaline and adrenaline by production of brain arachidonic acid in rats. Arachidonic acid is released mainly by phospholipase A2 (PLA2)-dependent pathway or phospholipase C (PLC)/diacylglycerol lipase-dependent pathway. In the present study, bombesin and GRP elevated plasma catecholamines in a dose-dependent manner (1 and 5 nmol/animal, i.c.v.), while neuromedin B (1, 5 and 10 nmol/animal, i.c.v.) had no effect in urethane-anesthetized rats (bombesin=GRP>>neuromedin B). The bombesin (1 nmol/animal, i.c.v.)-induced response was dose-dependently attenuated by [D-Phe6, des-Met14]-bombesin (6-14) ethylamide (bombesin BB2 receptor antagonist) (15.3 and 30.6 nmol/animal, i.c.v.) and also by U-73122 (PLC inhibitor) (10 and 100 nmol/animal, i.c.v.) and RHC-80267 (diacylglycerol lipase inhibitor) (1.3 and 2.6 micromol/animal, i.c.v.). However, D-Nal-cyclo[Cys-Tyr-d-Trp-Orn-Val-Cys]-Nal-NH2 (bombesin BB1 receptor antagonist) (30 and 100 nmol/animal, i.c.v.), mepacrine (PLA2 inhibitor) (1.1 and 2.2 micromol/animal, i.c.v.) and U-73343 (inactive analog of U-73122) (100 nmol/animal, i.c.v.) had no effect. These results suggest the involvement of brain PLC/diacylglycerol lipase in the brain bombesin BB2 receptor-mediated activation of sympatho-adrenomedullary outflow in rats.