GABA receptor subtypes involved in the neuronal mechanisms of baroreceptor reflex in the nucleus tractus solitarii of rabbits

Suzuki, Masahiko; Kuramochi, Tomoya; Suga, Toshio

doi:10.1016/0165-1838(93)90318-o

Cited by 32 publications

(20 citation statements)

References 23 publications

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“…Numerous studies have demonstrated that both GAR and GBR play an important role in the integration of baroreceptor afferent inputs and baroreflex function. Microinjection of the GAR agonist muscimol (24,37) or the GBR agonist baclofen (5,16,25,29) into the NTS produced a marked pressor response via inhibition of baroreflexes, elevation of sympathetic tone, and vasopressin release. Thus the preponderance of evidence indicates that the actions of GABA and ANG II within the NTS in BP and baroreflex regulation are very similar, suggesting that these factors may act via common cellular and/or intracellular mechanisms when influencing cardiovascular control.…”

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confidence: 99%

Angiotensin II increases GABA_B receptor expression in nucleus tractus solitarii of rats

Yao¹,

Sumners²,

O’Rourke³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Increasing evidence indicates that both the angiotensin II (ANG II) and gamma-aminobutyric acid (GABA) systems play a very important role in the regulation of blood pressure (BP). However, there is little information concerning the interactions between these two systems in the nucleus tractus solitarii (NTS). In the present study, we examined the effects of ANG II on GABAA and GABAB receptor (GAR and GBR) expression in the NTS of Sprague-Dawley rats. The direct effect of ANG II on GBR expression was determined in neurons cultured from NTS. Treatment of neuronal cultures with ANG II (100 nM, 5 h) induced a twofold increase in GBR1 expression, as detected with real-time RT-PCR and Western blots, but had no effect on GBR2 or GAR expression. In electrophysiological experiments, perfusion of neuronal cultures with the GBR agonist baclofen decreased neuronal firing rate by 39% and 63% in neurons treated with either PBS (control) or ANG II, respectively, indicating that chronic ANG II treatment significantly enhanced the neuronal response to GBR activation. In contrast, ANG II had no significant effect on the inhibitory action of the GAR agonist muscimol. In whole animal studies, intracerebroventricular infusion of ANG II induced a sustained increase in mean BP and an elevation of GBR1 mRNA and protein levels in the NTS. These results indicate that ANG II stimulates GBR expression in NTS neurons, and this could contribute to the central nervous system actions of ANG II that result in dampening of baroreflexes and elevated BP in the central actions of ANG II.

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confidence: 99%

Angiotensin II increases GABA_B receptor expression in nucleus tractus solitarii of rats

Yao¹,

Sumners²,

O’Rourke³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…The region of the NTS where baroreceptor afferents terminate contains a high density of both ␥-aminobutyric acid-A (GABA A ) and GABA B receptors. 1,2 A number of in vivo microinjection studies [3][4][5][6] as well as in vivo [7][8][9] and in vitro 10,11 single unit electrophysiological experiments have demonstrated that both GABA A and GABA B receptors play an important role in the integration of baroreceptor afferent inputs and baroreflex function. Since activation of GABA A receptors evokes postsynaptic inhibition and activation of GABA B receptors evokes both presynaptic and postsynaptic inhibition of NTS neurons, 10 microinjection of either GABA A or GABA B agonists into the NTS inhibits NTS neurons, which results in an inhibition of the baroreflex and an increase in mean arterial pressure (MAP).…”

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Enhanced γ-Aminobutyric Acid–B Receptor Agonist Responses and mRNA Within the Nucleus of the Solitary Tract in Hypertension

1999

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Abstract-␥-Aminobutyric acid-B (GABA B ) receptor function and regulation in the nucleus of the solitary tract (NTS) was examined in Sprague-Dawley rats made chronically (4 to 5 weeks) hypertensive with the one-kidney, figure-8 renal wrap model of hypertension. NTS microinjection of the GABA B agonist baclofen produced a pressor response that was enhanced in hypertensive rats compared with the response observed in sham-operated normotensive rats (36Ϯ4 mm Hg increase in mean arterial pressure in 8 hypertensive rats compared with 21Ϯ2 mm Hg increase in 7 sham-operated normotensive rats, Pϭ0.03). Responses to microinjection of GABA B antagonists (CGP-55845A and SCH-90511), the GABA A agonist muscimol, the GABA A antagonist bicuculline, and the GABA reuptake inhibitor nipecotic acid were not different comparing normotensive sham-operated and hypertensive rats. Renal sympathetic nerve responses to NTS microinjection of these drugs were not different in hypertensive compared with normotensive rats. Micropunches of the NTS were homogenized and reverse transcriptase-polymerase chain reaction was performed to examine mRNA levels for the GABA B receptor. There was a 3-fold increase in GABA B receptor mRNA levels in the caudal NTS of 7 chronically hypertensive rats compared with levels measured in 8 sham-operated normotensive rats (Pϭ0.01). In conclusion, chronic hypertension is associated with an upregulation of GABA B receptor function; however, the tonic activity of the system does not appear to be different between normotensive and hypertensive rats. The upregulation of GABA B receptor function might be due to an increased number of receptors, as suggested by the elevated levels of GABA B receptor mRNA measured in the NTS of hypertensive rats. All of these alterations suggest that hypertension is associated with dynamic changes in receptor-mediated mechanisms within the NTS, and these alterations could modify baroreflex regulation of cardiovascular function in hypertension. Key Words: kidney Ⅲ tractus solitarius Ⅲ hypertension, renal Ⅲ receptors, aminobutyric acid Ⅲ baclofen Ⅲ reverse transcriptase T he nucleus of the solitary tract (NTS) is the brain stem nucleus where baroreceptor afferent fibers make their initial synapse within the central nervous system. Therefore, information regarding the physiology and pharmacology of NTS neurons is critical to our understanding of baroreflex regulation of cardiovascular function. The region of the NTS where baroreceptor afferents terminate contains a high density of both ␥-aminobutyric acid-A (GABA A ) and GABA B receptors. 1,2 A number of in vivo microinjection studies 3-6 as well as in vivo 7-9 and in vitro 10,11 single unit electrophysiological experiments have demonstrated that both GABA A and GABA B receptors play an important role in the integration of baroreceptor afferent inputs and baroreflex function. Since activation of GABA A receptors evokes postsynaptic inhibition and activation of GABA B receptors evokes both presynaptic and postsynaptic inhibition of NTS neuron...

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“…In addition to the well-established role of tonically maintaining the excitability of sympathetic preganglionic neurons in the spinal cord (Guyenet, 1990;Reis et al, 1994), this medullary nucleus participates in BRR control of HR by modulating the excitatory inputs from the NTS to the parasympathetic preganglionic neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (NA) (Wang and Li, 1988). On the other hand, microiontophoretic application of GABA inhibits the excitability of the barosensitive neurons in the NTS (Feldman and Felder, 1991;Suzuki et al, 1993). Taken together with the present results, it is conceivable that GABA released in the NTS upon glutamatergic activation of the RVLM may reduce the excitatory inputs from the NTS to DMV and/or NA, resulting in an inhibition of reflex bradycardia in response to baroreceptor activation.…”

Section: Discussionmentioning

confidence: 99%

Rostral ventrolateral medulla suppresses reflex bradycardia by the release of gamma-aminobutyric acid in nucleus tractus solitarii of the rat

Len

Chan

2000

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GABA receptor subtypes involved in the neuronal mechanisms of baroreceptor reflex in the nucleus tractus solitarii of rabbits

Cited by 32 publications

References 23 publications

Angiotensin II increases GABA_B receptor expression in nucleus tractus solitarii of rats

Angiotensin II increases GABA_B receptor expression in nucleus tractus solitarii of rats

Enhanced γ-Aminobutyric Acid–B Receptor Agonist Responses and mRNA Within the Nucleus of the Solitary Tract in Hypertension

Rostral ventrolateral medulla suppresses reflex bradycardia by the release of gamma-aminobutyric acid in nucleus tractus solitarii of the rat

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GABA receptor subtypes involved in the neuronal mechanisms of baroreceptor reflex in the nucleus tractus solitarii of rabbits

Cited by 32 publications

References 23 publications

Angiotensin II increases GABAB receptor expression in nucleus tractus solitarii of rats

Angiotensin II increases GABAB receptor expression in nucleus tractus solitarii of rats

Enhanced γ-Aminobutyric Acid–B Receptor Agonist Responses and mRNA Within the Nucleus of the Solitary Tract in Hypertension

Rostral ventrolateral medulla suppresses reflex bradycardia by the release of gamma-aminobutyric acid in nucleus tractus solitarii of the rat

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Angiotensin II increases GABA_B receptor expression in nucleus tractus solitarii of rats

Angiotensin II increases GABA_B receptor expression in nucleus tractus solitarii of rats