The anticonvulsant and proconvulsant effects of α2-adrenoreceptor agonists are mediated by distinct populations of α2a-adrenoreceptors

Szot, Patricia; Lester, Matthew; Laughlin, M.L; Palmiter, Richard D.; Liles, L. Cameron; Weinshenker, David

doi:10.1016/j.neuroscience.2004.04.030

Cited by 58 publications

(37 citation statements)

References 41 publications

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“…both E139 and NE appear to produce their suppressant effects through action on ␣ 2 -adrenoceptors which have been reported to mediate the anticonvulsant effects of NE [12,18,33,34] . Consistent with previous reports on the anticonvulsant actions of NE [16,18,[35][36][37] , it suppressed the MS frequency and SB. Interestingly, unlike their mutually occlusive actions on PS amplitude, the presence of NE did not prevent E139 from further suppressing the MS frequency.…”

Section: Discussionsupporting

confidence: 92%

“…Also, the suppression of SB by NE occluded that of E139 further implicating an adrenergic mechanism. Finally, contrary to expectation, yohimbine almost completely wiped out the SB suggesting that NE, possibly acting on a subtype of ␣ 2 -adrenoceptor [16,34,38] , may promote epileptogenesis, i.e. have proconvulsant effects.…”

Section: Discussionmentioning

confidence: 57%

“…have proconvulsant effects. Pro-and anticonvulsant effects of NE acting on ␣ 2 -adrenoceptors have been reported to be mediated by distinct populations of the same subtype of ␣ 2 -adrenoceptors ( ␣ 2 A) located on presynaptic or postsynaptic sites [16] . Alternatively, the apparent anticonvulsant effect of yohimbine observed here may be due to its reported partial agonist action on some serotonin receptors [39] .…”

Section: Discussionmentioning

confidence: 99%

“…Norepinephrine (NE), the main endogenous ligand for these receptors in the central nervous system, is reported to have both convulsant and anticonvulsant properties [7][8][9][10][11][12][13][14][15] . These proconvulsant and anticonvulsant effects of NE are thought to depend on the receptor subtype that is activated [12,16] and possibly the extracellular concentration of NE [17,18] . The majority of reports appear to support an anticonvulsant role of NE.…”

mentioning

confidence: 99%

“…Pharmacological studies largely support this anticonvulsant role of NE [12,[21][22][23] . However, proconvulsant actions of NE have also been reported using various research approaches [16,17,24,25] .…”

mentioning

confidence: 99%

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Norepinephrine and E139 Interactions on Epileptiform Activity in the Rat Hippocampus in vitro

Kombian

Ananthalakshmi²,

Edafiogho³

2008

Med Princ Pract

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Objectives: We tested if E139, an anticonvulsant enaminone, interacts with norepinephrine (NE) to suppress population responses and chemically induced in vitro seizures in the rat hippocampus. Materials and Methods: Evoked field population spikes (PS) were recorded in the hippocampal CA1 area, and in vitro seizures were generated chemically using the zero Mg²⁺ model. Results: Low concentrations of E139 (≤10 µM) reversibly inhibited PS amplitude while high concentrations (≧100 µM) enhanced them. For example, E139 (10 µM) depressed the PS amplitude by –23.9 ± 2.3%, while 1 mM caused an enhancement. NE also depressed the PS by –34.5 ± 6.0% and prevented E139 from subsequently depressing the PS amplitude. UK 14304, a selective α₂-adrenoceptor agonist, also depressed the PS amplitude by –32.6 ± 9.4% and occluded E139 suppression. NE suppression of PS was blocked by phentolamine and yohimbine which also blocked the effect of E139. Prazosin, a selective α₁-adrenoceptor antagonist, did not block NE (–24.8 ± 6.9%) or E139 (–29.7 ± 6.1%) effects. Zero Mg²⁺ buffer transformed a single PS to multiple spikes (MS; 3–8 spikes) and also induced spontaneous bursts (SB; 5–20/min). NE suppressed the number of MS from 5.6 ± 0.3 to 3.8 ± 0.2. At its peak effect, E139 was able to further suppress the number of MS to 3.0 ± 0.3. Yohimbine did not change the number of MS but blocked the NE- and E139-induced suppression of MS. SB frequency was suppressed by NE (–60.8 ± 11.7%) which occluded E139 effects. Finally, SB were reversibly abolished by yohimbine (–94.5 ± 11.7%). Conclusion: E139 suppressed population responses and in vitro epileptiform activity by both adrenergic and non-adrenergic mechanisms.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Norepinephrine and E139 Interactions on Epileptiform Activity in the Rat Hippocampus in vitro

Kombian

Ananthalakshmi²,

Edafiogho³

2008

Med Princ Pract

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Ketogenic Diet and Drug-Resistant Epilepsy

Caraballo

2023

Pharmacoresistance in Epilepsy

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Presynaptic Metabotropic Receptors for Acetylcholine and Adrenaline/Noradrenaline

Gilsbach

Hein

2008

Handbook of Experimental Pharmacology

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Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline were first described more than three decades ago. Molecular cloning has resulted in the identification of five G protein-coupled muscarinic receptors (M(1) - M(5)) which mediate the biological effects of acetylcholine. Nine adrenoceptors (alpha(1ABD),alpha(2ABC),beta(123)) transmit adrenaline/noradrenaline signals between cells. The lack of sufficiently subtype-selective ligands has prevented identification of the physiological role and therapeutic potential of these receptor subtypes for a long time. Recently, mouse lines with targeted deletions for all muscarinic and adrenoceptor genes have been generated. This review summarizes the results from these gene-targeting studies with particular emphasis on presynaptic auto- and heteroreceptor functions of muscarinic and adrenergic receptors. Specific knowledge about the function of receptor subtypes will enhance our understanding of the physiological role of the cholinergic and adrenergic nervous system and open new avenues for subtype-selective therapeutic strategies.

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The anticonvulsant and proconvulsant effects of α2-adrenoreceptor agonists are mediated by distinct populations of α2a-adrenoreceptors

Cited by 58 publications

References 41 publications

Norepinephrine and E139 Interactions on Epileptiform Activity in the Rat Hippocampus in vitro

Norepinephrine and E139 Interactions on Epileptiform Activity in the Rat Hippocampus in vitro

Ketogenic Diet and Drug-Resistant Epilepsy

Presynaptic Metabotropic Receptors for Acetylcholine and Adrenaline/Noradrenaline

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