Dual regulation by ethanol of the inhibitory effects of ketamine on spinal NMDA-induced pressor responses in rats

Keng, Nien-Tzu; Lin, Hsun-Hsun; Lin, Huei-Ru; Hsieh, Wei-Kung; Lai, Chih-Chia

doi:10.1186/1423-0127-19-11

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…To determine the effects of Aβ on cardiovascular functions, we performed the intracerebroventricular injection of Aβ on NMDA receptor function in the RVLM. The resting MAP 81.37 ± 0.81 mmHg (n = 72) in urethane-anesthetized male SD rats was similar to our previous study [36,37]. Consecutive microinjection of NMDA (0.14 nmol, 100 nL) into the RVLM at intervals of 30 min induced an increase in MAP; the pressor responses were onset within 2 min and lasted for 10-15 min.…”

Section: Aβ Decreased Nmda-induced Pressor Responses In the Rvlmsupporting

confidence: 87%

Inhibition of NMDA Receptor Activation in the Rostral Ventrolateral Medulla by Amyloid-β Peptide in Rats

Islam,

Lai,

Wang

et al. 2023

Biomolecules

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N-methyl-D-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptors, are important in regulating sympathetic tone and cardiovascular function in the rostral ventrolateral medulla (RVLM). Amyloid-beta peptide (Aβ) is linked to the pathogenesis of Alzheimer’s disease (AD). Cerebro- and cardiovascular diseases might be the risk factors for developing AD. The present study examines the acute effects of soluble Aβ on the function of NMDA receptors in rats RVLM. We used the magnitude of increases in the blood pressure (pressor responses) induced by microinjection of NMDA into the RVLM as an index of NMDA receptor function in the RVLM. Soluble Aβ was applied by intracerebroventricular (ICV) injection. Aβ1-40 at a lower dose (0.2 nmol) caused a slight reduction, and a higher dose (2 nmol) showed a significant decrease in NMDA-induced pressor responses 10 min after administration. ICV injection of Aβ1-42 (2 nmol) did not affect NMDA-induced pressor responses in the RVLM. Co-administration of Aβ1-40 with ifenprodil or memantine blocked the inhibitory effects of Aβ1-40. Immunohistochemistry analysis showed a significant increase in the immunoreactivity of phosphoserine 1480 of GluN2B subunits (pGluN2B-serine1480) in the neuron of the RVLM without significant changes in phosphoserine 896 of GluN1 subunits (pGluN1-serine896), GluN1 and GluN2B, 10 min following Aβ1-40 administration compared with saline. Interestingly, we found a much higher level of Aβ1-40 compared to that of Aβ1-42 in the cerebrospinal fluid (CSF) measured using enzyme-linked immunosorbent assay 10 min following ICV administration of the same dose (2 nmol) of the peptides. In conclusion, the results suggest that ICV Aβ1-40, but not Aβ1-42, produced an inhibitory effect on NMDA receptor function in the RVLM, which might result from changes in pGluN2B-serine1480 (regulated by casein kinase II). The different elimination of the peptides in the CSF might contribute to the differential effects of Aβ1-40 and Aβ1-42 on NMDA receptor function.

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Section: Aβ Decreased Nmda-induced Pressor Responses In the Rvlmsupporting

confidence: 87%

Inhibition of NMDA Receptor Activation in the Rostral Ventrolateral Medulla by Amyloid-β Peptide in Rats

Islam,

Lai,

Wang

et al. 2023

Biomolecules

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“…The procedure for Western blot analysis of brain tissue was similar to that described in earlier studies [ 32 , 34 ]. Rats were sacrificed 30 min after oral gavage of ethanol or saline.…”

Section: Methodsmentioning

confidence: 99%

Role of neuronal nitric oxide synthase (nNOS) at medulla in tachycardia induced by repeated administration of ethanol in conscious rats

Situmorang

Lin

et al. 2018

J Biomed Sci

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BackgroundIntake of ethanol (alcohol) has been shown to influence cardiovascular function; the underlying brain mechanism remains unclear. Noting that nitric oxide (NO) system in the CNS is involved in the regulation of cardiovascular function, the present study examined the role of NO in medulla in ethanol-induced cardiovascular changes.MethodsEthanol was administered by oral gavage at dose of 3.2 g/kg once every day for 8 consecutive days. Changes in blood pressure (BP) and heart rate (HR) in response to ethanol were measured by radiotelemetry method in freely moving female Sprague-Dawley rats. NO modulators were applied by intracerebroventricular (ICV) injection. The protein levels of nitric oxide synthase (NOS) and NO content in rostroventral medulla were measured by Western blot and nitrate/nitrite colorimetric assay kit, respectively.ResultsEthanol intake had little effects on basal BP and HR following 8 consecutive day treatments. A significant increase in HR but not BP following ethanol intake was observed at 6th and 8th, but not at 1st and 4th day treatments as compared with saline group. A decrease in the protein expression of neuronal NOS (nNOS) but not inducible NOS or endothelial NOS and a decline in the level of NO in the medulla 30 min after ethanol administration was observed at 8th day treatment. ICV treatment with NO donors attenuated ethanol-induced tachycardia effects at 8th day treatment. Ethanol produced significantly tachycardia responses when ICV nNOS inhibitors were given at 1st day treatment.ConclusionOur results suggest that medulla nNOS/NO pathways play an important role in ethanol regulation of HR.

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“…Although in that paper we were not able to determine which of the many ion channels regulated by zinc were involved, several channels were raised as candidates. The pharmaceutical formulation of the metal plus vitamin supplements, as currently used, is a correct approach that may result in brain function improvement [ 133 ]. As to the use of nanostructured particles for zinc delivery to improve the pharmacokinetics of its administration, particularly its brain accessibility, it remains as an open question that deserves further experimentation.…”

Section: Biological Implications and Future Perspectivesmentioning

confidence: 99%

Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

Peralta

Huidobro‐Toro

2016

IJMS

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Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators.

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Dual regulation by ethanol of the inhibitory effects of ketamine on spinal NMDA-induced pressor responses in rats

Cited by 8 publications

References 45 publications

Inhibition of NMDA Receptor Activation in the Rostral Ventrolateral Medulla by Amyloid-β Peptide in Rats

Inhibition of NMDA Receptor Activation in the Rostral Ventrolateral Medulla by Amyloid-β Peptide in Rats

Role of neuronal nitric oxide synthase (nNOS) at medulla in tachycardia induced by repeated administration of ethanol in conscious rats

Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

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