Type I and II metabotropic glutamate receptor agonists and antagonists evoke cardiovascular effects after intrathecal administration in conscious rats

Li, Xiao C.; Beart, Philip M; Monn, James A.; Jones, Nicole M.; Widdop, Robert E

doi:10.1038/sj.bjp.0702850

Cited by 10 publications

(4 citation statements)

References 40 publications

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“…These structures are central to cardiac excitation and rhythmic control 6 35 -6 37 . The presence on GluRs in myocardium, conducting system, nerve fibers and intramural ganglia cells in all three species, strongly supports the view that these receptors may play a role in the physiology and pathophysiology of cardiac rhythm and excitation 90,638 . L-Glu increases the frequency of Ca ++ oscillations 639 , which have been positively correlated with increased contraction frequency in myocardial cells.…”

Section: Cardiovascularsupporting

confidence: 52%

A Review of Glutamate Receptors II: Pathophysiology and Pathology

Rousseaux

2008

J Toxicol Pathol

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Seventy years ago it was discovered that glutamate plays a central role in brain metabolism and is abundant in the brain. Glutamate was then found to be the principal excitatory neurotransmitter in the brain. As stated in the first article of this series, there are three families of ionotropic receptors with intrinsic cation permeable channels: Nmethyl-D-aspartate [NMDA], α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] and kainate [Ka].Among these there are three groups of metabotropic, G protein-coupled glutamate receptors [mGluR] that modify neuronal and glial excitability through G protein subunits acting on membrane ion channels and second messengers such as diacylglycerol and cAMP. There are also two glial glutamate transporters and three neuronal transporters in the brain. Although glutamate is the most abundant amino acid in the diet, there is no evidence for brain damage in humans resulting from dietary glutamate. However, a Ka analog, domoate, is sometimes ingested accidentally in blue mussels; this potent toxin causes limbic seizures, which can lead to hippocampal and related pathology and amnesia. Endogenous glutamate may contribute to the brain damage occurring acutely after status epilepticus, cerebral ischemia or traumatic brain injury by activating NMDA, AMPA or mGluR 1 receptors. Glutamate may also contribute to chronic neurodegeneration in such disorders as amyotrophic lateral sclerosis and Huntington's disease. In animal models of cerebral ischemia and traumatic brain injury, NMDA and AMPA receptor antagonists protect against acute brain damage and delayed behavioral deficits. Other clinical conditions that may respond to drugs acting on glutamatergic transmission include epilepsy, amnesia, anxiety, hyperalgesia and psychosis. In this second part of this review, we will explore those diseases in which the pathophysiology and pathology are associated, in part, with the glutamate system. (J Toxicol Pathol 2008; 21: 133-173)

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Section: Cardiovascularsupporting

confidence: 52%

A Review of Glutamate Receptors II: Pathophysiology and Pathology

Rousseaux

2008

J Toxicol Pathol

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“…The following doses were administered intrathecally to the lumbar spinal cord: NBQX, 0.5–4 µg (Zahn et al. , 1998); LY235959, 0.9–8.1 ng (Davis & Inturrisi, 2001); AIDA, 221 or 663 µg (Li et al. , 1999); L‐703606, 18–54 µg (Lofgren et al.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of tonic spinal glutamatergic activity induces antinociception in the rat

Tambeli

Parada

Levine

et al. 2002

Eur J of Neuroscience

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Inhibition of tonic activity in spino-supraspinal projection neurons induces heterosegmental antinociception that is mediated by opioid receptors in nucleus accumbens. To investigate the origin of this tonic activity, we evaluated the ability of inhibiting neurotransmission in the spinal cord to produce heterosegmental antinociception in the trigeminal nociceptive jaw-opening reflex (JOR) in the rat. Spinal intrathecal administration of calcium channel blockers attenuated the JOR, suggesting that the tonic spinal activity depends on synaptic input. To identify the excitatory neurotransmitter receptors involved, selective antagonists for AMPA/kainate, mGluR1, NMDA or NK1 receptors were administered intrathecally to the spinal cord. The AMPA/kainate and mGluR1 receptor antagonists, but not the NMDA or NK1 receptor antagonists, induced antinociception, which was antagonized by intra-accumbens administration of the selective micro -opioid receptor antagonist CTOP. Thus, inhibition of tonic spinal glutamatergic activity resulted in supraspinally mediated antinociception. As this antinociception occurred in the absence of interventions that would produce a facilitated nociceptive state, this tonic glutamatergic activity is important in setting nociceptive threshold.

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“…Furthermore, intrathecally adminisrtered (S)-3,5-DHPG increased mean arterial pressure (MAP) and heart rate (HR) (47). In a recent study (91) (S)-3,5-DHPG did not affect arterial blood pressure, but shortened the duration and decreased the amplitude of cardiac contraction, decreased heart rate, and had variable effects on coronary outflow.…”

Section: Cardiovascular Activitymentioning

confidence: 98%

(S)‐3,5‐DHPG: A Review

Wiśniewski

Car

2002

CNS Drug Reviews

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3,5-dihydroxyphenylglycine (3,5-DHPG) was the first agonist shown to be group I metabotropic glutamate receptor selective with its agonist effects residing exclusively in the S-isomer. Some results suggest that (S)-3,5-DHPG may be a partial agonist of mGluR 1a and mGluR 5a in neurons and astrocytes. It has been reported that (S)-3,5-DHPG can, under certain conditions, interact with NMDA receptors. (S)-3,5-DHPG exerts different effects on second messengers in adult and neonatal tissues. It stimulates phosphoinositide hydrolysis in a dose-dependent manner in both the adult and neonate hippocampus, inhibits stimulated cAMP levels in the adult and enhances the cAMP in the neonate. It is an effective antagonist of mGluRs linked to phospholipase D (PLD) in the adult and an agonist in the neonate brain or astrocyte cultures. (S)-3,5-DHPG induces elevation of [Ca 2+ ] i and regulates multiple subtypes of Ca 2+ channels. This agonist of group I mGluRs may modulate neurotransmitters release, reflecting the diversity of mechanisms involved. Depending on the dose, (S)-3,5-DHPG enhances or decreases excitatory postsynaptic potentials (EPSPs) and under appropriate conditions it can induce long-term depression (LTD) and long-term potentiation (LTP). Some studies suggested a therapeutic role for (S)-3,5-DHPG in neuronal injury, regulation of intestinal motility and secretion, learning and memory processes and in cardiovascular system.(S)-3,5-DHPG may be useful as a cognitive enhancing agent in memory impairment associated with ischemia or hypoxia. Recent investigations suggested possible beneficial effects of (S)-3,5-DHPG in Alzheimer's disease.

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Type I and II metabotropic glutamate receptor agonists and antagonists evoke cardiovascular effects after intrathecal administration in conscious rats

Cited by 10 publications

References 40 publications

A Review of Glutamate Receptors II: Pathophysiology and Pathology

A Review of Glutamate Receptors II: Pathophysiology and Pathology

Inhibition of tonic spinal glutamatergic activity induces antinociception in the rat

(S)‐3,5‐DHPG: A Review

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