Distribution and localisation of Gα proteins in the rostral ventrolateral medulla of normotensive and hypertensive rats: Focus on catecholaminergic neurons

Parker, Lindsay M.; Tallapragada, Vikram J.; Kumar, Natasha N.; Goodchild, Ann K.

doi:10.1016/j.neuroscience.2012.05.037

Cited by 6 publications

(8 citation statements)

References 64 publications

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“…Activation of cAMP-dependent pathways in the RVLM evoked sympathoexcitation and a pressor effect and bradycardia at cardiac vagal preganglionic neurons. This is in keeping with our finding that the G as subunit mRNA is abundant in the RVLM (Parker et al, 2012) and consistent with a postsynaptic site of action, as suggested previously in neonatal RVLM brain slice preparations, in which 8-Br-cAMP and the adenylyl cyclase activator forskolin increased the firing rate of RVLM "pacemaker" neurons in the presence of tetrodotoxin (Sun and Guyenet, 1990). Activation of G as -linked receptors in the RVLM using pituitary adenylate cyclase-activating peptide evokes sympathoexcitation and pressor responses, although reflex functions were unaffected (Farnham et al, 2012).…”

Section: Discussionsupporting

confidence: 92%

“…Despite this convergence, the expression and functions of G protein-related signaling molecules in controlling cardiovascular autonomic functions mediated by the ventrolateral medulla are poorly understood. We have previously demonstrated that mRNA for all G a proteins are expressed in the ventrolateral medulla, with G as most abundant (Parker et al, 2012). G as mRNA is present in all adrenergic C1 neurons, an important cardiovascular subpopulation within the region.…”

Section: Introductionmentioning

confidence: 97%

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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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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 97%

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 abundance of Gα s transcript compared to the other Gα subunits mirrors findings in a variety of supraspinal sites. 15,27–29 Persistent inflammatory nociception did not alter the relative abundance or levels of transcript of any of the six Gα subunits in the dorsal horn either four days or two weeks after injection of CFA. Whether this indicates that the Gα subunits are not differentially regulated, or that compensatory changes occur in transcription or stability, cannot be determined.…”

Section: Discussionmentioning

confidence: 88%

“…Table 1 lists the sequences of the forward and reverse primers for each of the six G protein subtypes and for the reference gene, Actb . The primers for Gnai1 , Gnai2 , Gnao , Gnas , and Actb are described elsewhere 14,15 and were validated by us. Primers for Gnaz and Gnaq were newly designed.…”

Section: Methodsmentioning

confidence: 99%

Peripheral inflammatory injury alters the relative abundance of Gα subunits in the dorsal horn of the spinal cord and in the rostral ventromedial medulla of male rats

et al. 2017

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A diverse array of G protein-coupled receptors (GPCRs) is implicated in the modulation of nociception. The efficacy and potency of several GPCR agonists change as a consequence of peripheral inflammatory injury. Whether these changes reflect alterations in expression of the G proteins themselves is not known. This study examined the expression of transcripts and proteins for the α subunits of three classes of heteromeric G proteins in the dorsal horn of the spinal cord and the rostral ventromedial medulla (RVM) of male rats four days and two weeks after intraplantar injection of complete Freund’s adjuvant (CFA) or saline. Levels of Gα transcript in the dorsal horn or RVM were unchanged by CFA treatment. However, in the dorsal horn, Gαi protein decreased in cytosolic and membrane fractions four days after CFA treatment. Levels of Gαz protein decreased in the membrane fraction. Levels of the other Gα subunits did not differ. Levels of the Gα subunits were unchanged two weeks after CFA treatment. In the RVM, Gαz protein levels decreased in the cytosolic fraction four days after CFA treatment. No other differences were observed. Two weeks after CFA, the levels for all Gα subunits trended higher in the RVM. These data indicate that peripheral inflammatory injury induces subtle changes in the abundance of Gα subunits that is specific with respect to class, subcellular compartment, tissue, and time after injury. These changes have the potential to alter the balance of the different subcellular signaling pathways through which GPCR agonists act to modulate nociception.

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“…Parker et al. () has previously shown that G α i2 and G α O are the most ubiquitous inhibitory G proteins in the RVLM. In keeping with this, our data suggest an important functional role for G α O .…”

Section: Discussionmentioning

confidence: 98%

The role of Gα_O‐mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability

Ang

Abramowitz

Birnbaumer

et al. 2016

Physiological Reports

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The heart is controlled by the sympathetic and parasympathetic limbs of the autonomic nervous system with inhibitory signaling mechanisms recruited in both limbs. The aim of this study was to determine the role of inhibitory heterotrimeric G proteins in the central nervous mechanisms underlying autonomic control of the heart and its potential role in arrhythmogenesis. Mice with conditional deletion of the inhibitory heterotrimeric G protein Gα O in the presympathetic area of the rostral ventral lateral medulla (RVLM) were generated to determine the role of GαO‐mediated signalling in autonomic control and electrophysiological properties of the heart. Gα O deletion within the RVLM was not associated with changes in heart rate (HR) or the arterial blood pressure at rest (home cage, normal behavior). However, exposure to stressful conditions (novel environment, hypoxia, or hypercapnia) in these mice was associated with abnormal HR responses and an increased baroreflex gain when assessed under urethane anesthesia. This was associated with shortening of the ventricular effective refractory period. This phenotype was reversed by systemic beta‐adrenoceptor blockade, suggesting that Gα O depletion in the RVLM increases central sympathetic drive. The data obtained support the hypothesis that Gα O‐mediated signaling within the presympathetic circuits of the RVLM contributes to the autonomic control of the heart. Gα O deficiency in the RVLM has a significant impact on cardiovascular responses to stress, cardiovascular reflexes and electrical properties of the heart.

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Distribution and localisation of Gα proteins in the rostral ventrolateral medulla of normotensive and hypertensive rats: Focus on catecholaminergic neurons

Cited by 6 publications

References 64 publications

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

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

Peripheral inflammatory injury alters the relative abundance of Gα subunits in the dorsal horn of the spinal cord and in the rostral ventromedial medulla of male rats

The role of Gα_O‐mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability

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Distribution and localisation of Gα proteins in the rostral ventrolateral medulla of normotensive and hypertensive rats: Focus on catecholaminergic neurons

Cited by 6 publications

References 64 publications

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

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

Peripheral inflammatory injury alters the relative abundance of Gα subunits in the dorsal horn of the spinal cord and in the rostral ventromedial medulla of male rats

The role of GαO‐mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability

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The role of Gα_O‐mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability