β-Adrenergic Regulation of Adenosine 3′,5′-Monophosphate Concentration in Brain Microvessels

Herbst, Timothy; Raichle, Marcus E.; Ferrendelli, James A.

doi:10.1126/science.34879

Cited by 116 publications

(18 citation statements)

References 33 publications

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“…Thus, LC stimulation increases the permeability of the blood-brain barrier to water (25), whereas LC lesion is associated with increased "leakiness" of the barrier to macromolecules such as albumin (26). The presence of adrenergic receptors on cerebral microvessels (22,27,28) and the relationship between these receptors and cyclic AMP generation (29,30) indicate that cerebral microvessels are capable of recognizing and reacting to adrenergic agonists. The present results suggest that Na+/K+-ATPase activity of these microvessels is modulated by intrinsic norepinephrine innervation from the LC.…”

Section: Resultsmentioning

confidence: 99%

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Harik¹

1986

Proc. Natl. Acad. Sci. U.S.A.

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The active transport of Na+ and K+ across the blood-brain barrier by the membrane-bound enzyme Na+/K+-activated ATPase of brain microvessel endothelial cells has a major role in the maintenance of brain water and electrolyte homeostasis. To test whether the putative noradrenergic innervation of cerebral microvessels from the nucleus locus ceruleus contributes to the regulation of Na+/K+-ATPase activity of the blood-brain barrier, specific [3H]ouabainbinding studies were performed on cerebral microvessels and crude cortical membranes obtained from Wistar rats with unilateral 6-hydroxydopamine lesion of the nucleus locus ceruleus. Such lesion depleted norepinephrine by about 90% in the ipsilateral cerebral cortex without affecting the contralateral cortex.[3lH]Ouabain binding to membranes of cerebral cortex and the cerebral microvessels was specific and saturable. The maximal ouabain-binding capacity in microvessels of the ipsilateral, norepinephrine-depleted, cerebral cortex was reduced by about 40%, without change in the affinity of binding.[3H]Ouabain binding to crude membrane fractions of the cerebral cortex was not significantly affected by locus ceruleus lesion. The results suggest that Na+/K+-ATPase activity of cerebral microvessels, and the consequent transport of Na+ and K+ across the blood-brain barrier, is modulated by noradrenergic innervation from the locus ceruleus.

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Section: Resultsmentioning

confidence: 99%

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Harik¹

1986

Proc. Natl. Acad. Sci. U.S.A.

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“…In particular this has been demonstrated for VIP [10,11], acetylcholine [10], cholecystokinin [12,13] and NA [14,15]. In addition, pharmacological studies have demonstrated the presence of receptors for NA and VIP, coupled to cAMP-generating systems [16][17][18] in intra parenchymal microvessel preparations. In a recent study [3] performed in purified preparations of mouse cerebral cortex consisting of primary astrocyte cultures, intra parenchymal microvessels and synaptosomal mem branes respectively, three VIP receptor subtypes, with differential cellular localization, were identified (table 1) .…”

Section: Introductionmentioning

confidence: 97%

Neurotransmitters Regulate Energy Metabolism in Astrocytes: Implications for the Metabolic Trafficking between Neural Cells

et al. 1993

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In recent years a vast array of experimental evidence has indicated the presence of functional receptors for neurotransmitters on nonneuronal cells, in particular astrocytes. The two neurotransmitters vasoactive intestinal peptide (VIP) and noradrenaline (NA) exert profound, receptor-mediated, metabolic actions on astrocytes. Thus both neurotransmitters stimulate glycogenolysis in primary astrocyte cultures, with EC₅₀s of 3 and 20 nM respectively. Astrocytes display basal glucose utilization rates ranging between 3 and 9 nmol/mg prot/min, a value that is remarkably close to glucose utilization of cerebral cortical grey matter as determined by the 2-deoxyglucose autoradiographic technique. NA markedly enhances glucose uptake and phosphorylation by astrocytes, with an EC₅₀ of 1 µM. The metabolic substrate that is released by astrocytes is predominantly lactate and not glucose. Since lactate can support neuronal activity and synaptic function in vitro, the possibility should be considered that glucose uptake by the brain parenchyma occurs predominantly into astrocytes which subsequently release lactate for the use of neurons.

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“…Buonassisi and Venter (19) studied endothelium cultured from rabbit aorta and found a catecholamine-stimulated cyclic AMP response that could be fully blocked by the 8-adrenergic antagonist propanolol. Similarly, Herbst and his associates (20) found that norepinephrine increased cyclic AMP formation in an incubated suspension of brain microvessels that could be abolished with propanolol.…”

Section: Discussionmentioning

confidence: 75%

Diminished Polymorphonuclear Leukocyte Adherence

1980

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A B S T R A C T To investigate the biochemical and cellular basis for the rise in polymorphonuclear leukocyte (PMN) count during epinephrine administration, PMN from subjects receiving epinephrine were studied for their capacity to adhere to nylon wool fibers and endothelial cell monolayers. After administration of epinephrine, the PMN count increased by 80% at 5 min, and isolated PMN adherence to nylon fibers fell from a base line of44±2-18+3%. In contrast, when subjects were infused with the 13-antagonist propanolol before receiving epinephrine, the PMN count failed to rise and PMN adherence was normal. Exposure of PMN endothelial cell monolayers to 0.1 ,uM epinephrine led to diminished PMN adherence that could be blocked by 10 uM propanolol but not by 10 ,uM phentolamine. Sera obtained from subjects 5 min after receiving epinephrine or from supernates derived from endothelial cell monolayers exposed to 90 nM epinephrine inhibited PMN adherence to nylon fibers. Addition of anticyclic AMP antisera but not anticyclic guanosine monophosphate antisera to the postepinephrine sera or to the postepinephrine supernate derived from the endothelial cell monolayers abolished their inhibitory effect of PMN adherence to nylon fibers. In contrast, direct exposure of PMN to epinephrine failed to affect their adherent properties. Because it has been previously shown that endothelial cells contain 18-receptors and respond to catecholamines by raising their intracellular concentrations ofcyclic AMP, and that PMN adherence is attenuated by cyclic AMP, it would appear that diminished PMN adherence after epinephrine administration is mediated through endothelial cell ,3-receptor activity, which in turn impairs PMN margination in vivo and could account for the rise in circulating PMN.

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β-Adrenergic Regulation of Adenosine 3′,5′-Monophosphate Concentration in Brain Microvessels

Cited by 116 publications

References 33 publications

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

Neurotransmitters Regulate Energy Metabolism in Astrocytes: Implications for the Metabolic Trafficking between Neural Cells

Diminished Polymorphonuclear Leukocyte Adherence

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