Expression and functions of β1- and β2-adrenergic receptors on the bulbospinal neurons in the rostral ventrolateral medulla

Oshima, Naoki; Onimaru, Hiroshi; Yamamoto, Kojiro; Takechi, Hanako; Nishida, Yasuhiro; Oda, Takashi; Kumagai, Hiroo

doi:10.1038/hr.2014.112

Cited by 15 publications

(9 citation statements)

References 47 publications

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“…The mechanism of the little-to-no effect of adrenergic receptor agonist in vitro assay is not clear. Adrenergic receptors are expressed in the central nervous system and peripheral nervous system involving in the regulation of various physiological functions [ 29 , 30 ]. Glucocorticoids are the major regulators of CYP450, and their release are affected by the adrenergic signaling pathway [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway

Zhou

Tan

et al. 2017

Oncotarget

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Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats. Forty-nine genes in liver of model rats displayed significant difference comparing to control rats. The differentially expressed genes enriched in the drug metabolism and steroid hormone biosynthesis pathway significantly, and Nr1i3 matched 335 connectivity genes. CAR and Ugt1a1 protein expression were enhanced significantly in liver of model rats. The mRNA expression of Ugt1a1 and Nr1i2 were increased 2 and 4 times respectively with dexamethasone (DEX) and 8-Br-cAMP co-treatment in BRL 3A cells. The protein expression of PXR was up-regulated, too. However, RU486 reversed the up-regulated effect. The adrenergic receptor agonists had little impact on the DMEs in BRL 3A. Our data suggested that CUMS-induced depression might up-regulate DMEs expression via glucocorticoid signaling pathway, and accelerate the fate of the repaglinide in spontaneous diabetes rats.

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Section: Discussionmentioning

confidence: 99%

Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway

Zhou

Tan

et al. 2017

Oncotarget

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“…On cAMP Signaling in the Ventrolateral Medulla the other hand, cardiac vagal nerve activity is increased by systemic adenosine (da Silva et al, 2012) or by activation of b-adrenergic receptors, specifically b1, which reduces GABAergic and glycinergic (as well as glutamatergic) conductances at cardiac vagal preganglionic neurons (Bateman et al, 2012). Recently, b1 and b2 receptors have been identified on putative presympathetic RVLM neurons, and their selective activation evoked depolarization and hyperpolarization, respectively (Oshima et al, 2014). These data suggest that cAMP-dependent signaling can be elicited by catecholamine release in the ventrolateral medulla.…”

Section: Discussionmentioning

confidence: 84%

“…Nevertheless the findings here suggest that a neurotransmitter acting via G aslinked receptor/s is active in the ventrolateral medulla. One possibility is a catecholamine acting at b receptors where, at least in the neonatal RVLM, b2-receptor blockade depolarized neurons (Oshima et al, 2014). However, an alternative explanation could be that such a receptor is constitutively active (Milligan, 2003;Costa and Cotecchia, 2005) and candidates that are G as -linked in the RVLM include the H2 and melanocortin 3/4 receptors (Granata and Reis, 1987;Kawabe et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Tonically Active cAMP-Dependent Signaling in the Ventrolateral Medulla Regulates Sympathetic and Cardiac Vagal Outflows

Tallapragada

Hildreth

Burke

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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The ventrolateral medulla contains presympathetic and vagal preganglionic neurons that control vasomotor and cardiac vagal tone, respectively. G protein-coupled receptors influence the activity of these neurons. G as activates adenylyl cyclases, which drive cyclic adenosine monophosphate (cAMP)-dependent targets: protein kinase A (PKA), the exchange protein activated by cAMP (EPAC), and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. The aim was to determine the cardiovascular effects of activating and inhibiting these targets at presympathetic and cardiac vagal preganglionic neurons. Urethane-anesthetized rats were instrumented to measure splanchnic sympathetic nerve activity (sSNA), arterial pressure (AP), heart rate (HR), as well as baroreceptor and somatosympathetic reflex function, or were spinally transected and instrumented to measure HR, AP, and cardiac baroreflex function. All drugs were injected bilaterally. In the rostral ventrolateral medulla (RVLM), Sp-cAMPs and 8-Br-cAMP, which activate PKA, as well as 8-pCPT, which activates EPAC, increased sSNA, AP, and HR. Sp-cAMPs also facilitated the reflexes tested. Sp-cAMPs also increased cardiac vagal drive and facilitated cardiac baroreflex sensitivity. Blockade of PKA, using RpcAMPs or H-89 in the RVLM, increased sSNA, AP, and HR and increased HR when cardiac vagal preganglionic neurons were targeted. Brefeldin A, which inhibits EPAC, and ZD7288, which inhibits HCN channels, each alone had no effect. Cumulative, sequential blockade of all three inhibitors resulted in sympathoinhibition. The major findings indicate that G as -linked receptors in the ventral medulla can be recruited to drive both sympathetic and parasympathetic outflows and that tonically active PKA-dependent signaling contributes to the maintenance of both sympathetic vasomotor and cardiac vagal tone.

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“…[ 67 – 69 ] The β 2 -ARs can also couple to G i protein to inhibit the downstream effectors. [ 70 – 72 ]…”

Section: Introductionmentioning

confidence: 99%

Targeting modulation of noradrenalin release in the brain for amelioration of REMS loss-associated effects

Singh

Mallick

2015

Journal of Translational Internal Medicine

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Rapid eye movement sleep (REMS) loss affects most of the physiological processes, and it has been proposed that REMS maintains normal physiological processes. Changes in cultural, social, personal traits and life-style severely affect the amount and pattern of sleep, including REMS, which then manifests symptoms in animals, including humans. The effects may vary from simple fatigue and irritability to severe patho-physiological and behavioral deficits such as cognitive and behavioral dysfunctions. It has been a challenge to identify a molecule(s) that may have a potential for treating REMS loss-associated symptoms, which are very diverse. For decades, the critical role of locus coeruleus neurons in regulating REMS has been known, which has further been supported by the fact that the noradrenalin (NA) level is elevated in the brain after REMS loss. In this review, we have collected evidence from the published literature, including those from this laboratory, and argue that factors that affect REMS and vice versa modulate the level of a common molecule, the NA. Further, NA is known to affect the physiological processes affected by REMS loss. Therefore, we propose that modulation of the level of NA in the brain may be targeted for treating REMS loss-related symptoms. Further, we also argue that among the various ways to affect the release of NA-level, targeting α2 adrenoceptor autoreceptor on the pre-synaptic terminal may be the better option for ameliorating REMS loss-associated symptoms.

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Expression and functions of β1- and β2-adrenergic receptors on the bulbospinal neurons in the rostral ventrolateral medulla

Cited by 15 publications

References 47 publications

Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway

Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway

Tonically Active cAMP-Dependent Signaling in the Ventrolateral Medulla Regulates Sympathetic and Cardiac Vagal Outflows

Targeting modulation of noradrenalin release in the brain for amelioration of REMS loss-associated effects

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