GABA_B receptor in the hypothalamic paraventricular nucleus mediates β-adrenoceptor activation-induced elevation of plasma noradrenaline in rats

Abstract

In the brain, various neurotransmitters such as noradrenaline and GABA regulate the peripheral sympathetic functions. Previously, it has been reported that both of β-adrenoceptor activation and GABA_B receptor activation in the brain are involved in the elevation of plasma noradrenaline level. However, it is unknown whether or not these pathways interact with each other as part of the central regulation of plasma noradrenaline level. In the present study, we examined the interrelationship between the central actions of β-adrenoceptor activation and GABA_B receptor activation in plasma noradrenaline responses using urethane-anesthetized rats. Intracerebroventricular pretreatment with the GABA_A receptor antagonist bicuculline did not affect the β-adrenoceptor agonist isoproterenol-induced elevation of plasma noradrenaline level. On the other hand, the pretreatment with the GABA_B receptor antagonist CGP 35348 dose-dependently suppressed the isoproterenol-induced elevation of plasma level of noradrenaline, but not adrenaline. Intracerebroventricular pretreatment with the β-adrenoceptor antagonist propranolol did not change the GABA_B receptor agonist baclofen-induced elevation of plasma noradrenaline level. Next, agonist for GABA_B receptor or β-adrenoceptor was microinjected unilaterally into the paraventricular hypothalamic nucleus (PVN), the major integrative center for sympathetic regulation in the brain. Both of microinjections of baclofen and isoproterenol elevated plasma level of noradrenaline, but not adrenaline. Finally, we examined central effects of β-adrenoceptor activation on GABA release in the PVN. Intracerebroventricular administration of isoproterenol increased GABA content in the PVN dialysates. Our results suggest that activation of β-adrenoceptor in the brain, probably in the PVN, induces GABA release in the PVN and then released GABA activates GABA_B receptor in the PVN, resulting in the elevation of plasma noradrenaline level.