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GABAB receptors in the hypothalamic paraventricular nucleus mediate β-adrenoceptor-induced elevations of plasma noradrenaline in rats.

Abstract：

:In the brain, various neurotransmitters such as noradrenaline and GABA regulate peripheral sympathetic functions. Previously, it has been reported that both β-adrenoceptor activation and GABAB receptor activation in the brain are involved in the elevation of plasma noradrenaline levels. However, it is unknown whether these pathways interact with each other. In the present study, we examined the relationship between the central actions of β-adrenoceptor activation and GABAB receptor activation with regard to plasma noradrenaline responses using urethane-anesthetized rats. Intracerebroventricular pretreatment with the GABAA receptor antagonist bicuculline did not affect the β-adrenoceptor agonist isoproterenol-induced elevation of plasma noradrenaline levels. In contrast, pretreatment with the GABAB receptor antagonist CGP 35348 suppressed the isoproterenol-induced elevation of noradrenaline levels. Intracerebroventricular pretreatment with the β-adrenoceptor antagonist propranolol did not alter the GABAB receptor agonist baclofen-induced elevation of plasma noradrenaline levels. We next examined the central effects of β-adrenoceptor activation on GABA release in the paraventricular hypothalamic nucleus (PVN), the major integrative center for sympathetic regulation in the brain. Intracerebroventricular administration of isoproterenol increased GABA content in PVN dialysates. In addition, baclofen microinjected unilaterally into the PVN resulted in elevated plasma levels of noradrenaline, but not adrenaline. Finally, unilateral blockade of GABAB receptors in the PVN suppressed the isoproterenol-induced elevation of plasma noradrenaline level. Our results suggest that activation of β-adrenoceptors in the brain, likely in the PVN, induces GABA release in the PVN, which in turn activates GABAB receptors in the PVN, leading to elevated plasma noradrenaline.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Yamaguchi N,Mimura K,Okada S

doi

10.1016/j.ejphar.2019.01.029

subject

Has Abstract

pub_date

2019-04-05 00:00:00

pages

88-95

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(19)30046-9

journal_volume

848

pub_type

杂志文章

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GABAB receptors in the hypothalamic paraventricular nucleus mediate β-adrenoceptor-induced elevations of plasma noradrenaline in rats.