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

In the brain, various neurotransmitters such as noradrenaline and GABA regulate peripheral sympathetic functions. Previously, it has been reported that both beta-adrenoceptor activation and GABA(B) 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 beta-adrenoceptor activation and GABA(B) receptor activation with regard to plasma noradrenaline responses using urethane-anesthetized rats. Intracerebroventricular pretreatment with the GABA(A) receptor antagonist bicuculline did not affect the beta-adrenoceptor agonist isoproterenol-induced elevation of plasma noradrenaline levels. In contrast, pretreatment with the GABA(B) receptor antagonist CGP 35348 suppressed the isoproterenol-induced elevation of noradrenaline levels. Intracerebroventricular pretreatment with the beta-adrenoceptor antagonist propranolol did not alter the GABA(B) receptor agonist baclofen-induced elevation of plasma noradrenaline levels. We next examined the central effects of beta-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 GABA(B) receptors in the PVN suppressed the isoproterenol-induced elevation of plasma noradrenaline level. Our results suggest that activation of beta-adrenoceptors in the brain, likely in the PVN, induces GABA release in the PVN, which in turn activates GABA(B) receptors in the PVN, leading to elevated plasma noradrenaline.