Increased expression of M2 muscarinic receptor mRNA and binding sites in the rostral ventrolateral medulla of spontaneously hypertensive rats

Gattu, Mahanandeeshwar; Wei, Jian Wen; Pauly, James R.; Urbanawiz, Shanna; Buccafusco, Jerry J.

doi:10.1016/s0006-8993(97)00126-1

Cited by 13 publications

(12 citation statements)

References 23 publications

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“…We have confirmed the findings of Gattu et al [26] that all five muscarinic receptors are present in the ventral medulla of both SHR and WKY. Using real time RT-PCR overcame the limitations of end-point detection in RT-PCR used previously.…”

Section: Discussionsupporting

confidence: 92%

“…Using real time RT-PCR overcame the limitations of end-point detection in RT-PCR used previously. Confirming previous data [26], we have demonstrated that M2 receptor mRNA expression is almost two-fold greater in the RVM of SHR compared with WKY. In contrast [26], we describe for the first time that the M4 receptor transcription is reduced by 50% in the RVM of SHR compared with WKY, but found no differences in M3 receptor mRNA expression.…”

Section: Discussionsupporting

confidence: 91%

“…In SHR, there is more M2 receptor mRNA in a large brainstem area that included the RVLM compared with normotensive controls [26]. We have recently demonstrated that a subpopulation of bulbospinal, non-C1 neurons in the RVLM of normotensive animals contains M2 receptor mRNA [3].…”

Section: Introductionmentioning

confidence: 92%

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Differential muscarinic receptor gene expression levels in the ventral medulla of spontaneously hypertensive and Wistar–Kyoto rats: role in sympathetic baroreflex function

Kumar

Padley²,

Pilowsky³

et al. 2009

Journal of Hypertension

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These data indicate that enhanced pressor responses in SHR, following centrally mediated mAChR activation, are not associated with RVLM-mediated constriction of the splanchnic circulation or effects on the sympathetic baroreflex, but could reflect modified mAChR gene expression elsewhere. RVLM-dependent splanchnic sympathetic nerve activity effects, evoked by mAChR activation, are not mediated by the differential M2/M4 receptor mRNA levels identified in SHR compared with WKY.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

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Differential muscarinic receptor gene expression levels in the ventral medulla of spontaneously hypertensive and Wistar–Kyoto rats: role in sympathetic baroreflex function

Kumar

Padley²,

Pilowsky³

et al. 2009

Journal of Hypertension

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“…We have further demonstrated that mRNA for all 5 mAChR subtypes was present in the RVLM, confirming earlier studies in WKY and SHR rats. 47 Our results suggest that different or multiple mAChR subtypes may be expressed by sympathoexcitatory RVLM neurons.…”

Section: Padley Et Al Cholinergic Inputs To Rvlm In Central Commandmentioning

confidence: 66%

Central Command Regulation of Circulatory Function Mediated by Descending Pontine Cholinergic Inputs to Sympathoexcitatory Rostral Ventrolateral Medulla Neurons

Padley

Kumar

et al. 2007

Circulation Research

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Abstract-Central command is a feedforward neural mechanism that evokes parallel modifications of motor and cardiovascular function during arousal and exercise. The neural circuitry involved has not been elucidated. We have identified a cholinergic neural circuit that, when activated, mimics effects on tonic and reflex control of circulation similar to those evoked at the onset of and during exercise. Central muscarinic cholinergic receptor (mAChR) activation increased splanchnic sympathetic nerve activity (SNA) as well as the range and gain of the sympathetic baroreflex via activation of mAChR in the rostral ventrolateral medulla (RVLM) in anesthetized artificially ventilated SpragueDawley rats. RVLM mAChR activation also attenuated and inhibited the peripheral chemoreflex and somatosympathetic reflex, respectively. Cholinergic terminals made close appositions with a subpopulation of sympathoexcitatory RVLM neurons containing either preproenkephalin mRNA or tyrosine hydroxylase immunoreactivity. M2 and M3 receptor mRNA was present postsynaptically in only non-tyrosine hydroxylase neurons. Cholinergic inputs to the RVLM arise only from the pedunculopontine tegmental nucleus. Chemical activation of this region produced increases in muscle activity, SNA, and blood pressure and enhanced the SNA baroreflex; the latter effect was attenuated by mAChR blockade. These findings indicate a novel role for cholinergic input from the pedunculopontine tegmental nucleus to the RVLM in central cardiovascular command. This pathway is likely to be important during exercise where a centrally evoked facilitation of baroreflex control of the circulation is required to maintain blood flow to active muscle. (Circ Res. 2007;100:284-291.)Key Words: baroreflex Ⅲ exercise Ⅲ chemoreflex Ⅲ somatosympathetic A distinct pattern of tonic and reflex cardiovascular adjustments is mediated by central command to ensure appropriate muscle and organ perfusion during different arousal or behavioral states, such as sleep and exercise. [1][2][3] Limited evidence implicates some regions within the pons and hypothalamus that could provide descending input to cardiovascular control sites 4 -6 ; however, the neural circuitry and neurotransmitters involved are yet to be elucidated.Activation of the central cholinergic system has a profound effect on cardiovascular and other autonomic functions. [7][8][9][10][11][12][13][14][15][16][17][18] Systemic or central administration of acetylcholinesterase inhibitors or muscarinic agonists increases blood pressure, 7-11 lowers body temperature, 12 and alters respiration. 13,14 Pressor responses can be evoked via activation of muscarinic receptors (mAChR) within several cardiovascular nuclei, including the posterior hypothalamus, 7 nucleus of the solitary tract, 15 and rostral ventrolateral medulla (RVLM). 10,11 Effects of central mAChR activation on cardiovascular reflexes are less well understood. 8,16,17 Sympathoexcitatory and hypertensive effects of intravenously administered physostigmine are largely mediated by ...

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“…Non-specific binding was determined in the presence of 40 µM atropine in the incubation system. Schwab et al (1992) and Gattu et al (1997), respectively. The brain sections were thawed and dried at room temperature, then incubated with cold 10 mM phosphate buffer (pH 7.4) for 30 min.…”

Section: Acetylcholinesterase Activity By Histochemistry Assaymentioning

confidence: 99%

Roles of .Mu.-Opioid Receptors in Development of Tolerance to Diisopropylfluorophosphate (Dfp)

Tien

Fan

et al. 2005

J. Toxicol. Sci.

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-Anatomical evidence indicates that cholinergic and opioidergic systems are co-localized and acting on the same neuron. However, the regulatory mechanisms between cholinergic and opioidergic system have not been well characterized. In the present study, the potential involvement of µ-opioid receptors in mediating the changes of toxic signs and muscarinic receptor binding after administration of irreversible anti-acetylcholinesterase diisopropylfluorophosphate (DFP) was investigated. DFP (1 mg/kg/day, subcutaneous injection, s.c.)-induced tremors and chewing movements were monitored during the 28-day treatment period in µ-opioid receptor knockout and wild type mice. Autoradiographic studies of total, M1, and M2 muscarinic receptors were conducted using [ ]-AF-DX384 as ligands, respectively. DFP-induced tremors in both µ-opioid receptor knockout and wild type mice showed tolerance development. However, DFP-induced tremors in µ-opioid receptor knockout mice showed delayed tolerance development than that of DFP-treated wild type controls. DFPinduced chewing movements in both µ-opioid receptor knockout and wild type mice failed to show development of tolerance after four weeks of treatment. M2 muscarinic receptor binding of DFP-treated µ-opioid receptor knockout mice was significantly decreased than that of the DFP-treated wild type controls in the striatum, but not in the cortex and hippocampus. However, there were no significant differences in total and M1 muscarinic receptor binding between DFP-treated µ-opioid receptor knockout and wild type mice in the cortex, striatum and hippocampus. These studies indicate that µ-opioid receptors play an important role through the striatal M2 muscarinic receptors to regulate the development of tolerance to DFP-induced tremors.

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Increased expression of M2 muscarinic receptor mRNA and binding sites in the rostral ventrolateral medulla of spontaneously hypertensive rats

Cited by 13 publications

References 23 publications

Differential muscarinic receptor gene expression levels in the ventral medulla of spontaneously hypertensive and Wistar–Kyoto rats: role in sympathetic baroreflex function

Differential muscarinic receptor gene expression levels in the ventral medulla of spontaneously hypertensive and Wistar–Kyoto rats: role in sympathetic baroreflex function

Central Command Regulation of Circulatory Function Mediated by Descending Pontine Cholinergic Inputs to Sympathoexcitatory Rostral Ventrolateral Medulla Neurons

Roles of .Mu.-Opioid Receptors in Development of Tolerance to Diisopropylfluorophosphate (Dfp)

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