Effects of the Areca nut constituents arecaidine and guvacine on the action of GABA in the cat central nervous system

Lodge, David; Johnston, G. A. R.; Curtis, D. R.; Brand, S.

doi:10.1016/0006-8993(77)90075-0

Cited by 100 publications

(38 citation statements)

References 13 publications

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“…The difference between muscimol and GABA after administration for 5 min might thus reflect the differing efficiencies of the cellular uptake processes which transport these two amino acids from the extracellular space (Johnston, Kennedy & Lodge, 1978), although the actions of muscimol and GABA in vivo are similarly enhanced by inhibitors of the in vitro uptake of GABA (Lodge, Curtis & Johnston, 1978). This assumption regarding the importance of cellular uptake in determining the time course of action of amino acids would predict a prolonged depressant effect for taurine, an amino acid apparently not taken up by spinal tissue (Lodge, Johnston, Curtis & Brand, 1977), for isoguvacine, which is not a substrate for GABA transport processes (KrogsgaardLarsen et al 1977;, and for 3-aminopropane sulphonate, a relatively weak inhibitor of GABA uptake (Beart & Johnston, 1973). It should be pointed out, however, that the absence of significant interference by an amino acid with the cellular uptake of GABA does not exclude uptake by another amino acid transport mechanism.…”

Section: Methodsmentioning

confidence: 99%

The excitation and depression of spinal neurones by ibotenic acid.

Curtis¹,

Lodge²,

McLennan³

1979

The Journal of Physiology

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SUMMARY1. The firing of spinal interneurones and Renshaw cells by microelectrophoretic (± )-ibotenate, which was approximately eight times more active as an excitant than L-glutamate, was followed by prolonged depression of the sensitivity of the neurones to excitant amino acids and acetylcholine.2. The depression, which lasted for 15-30 min when ibotenate was ejected for 3-6 min, was blocked by the GABA-antagonist bicuculline methochloride, and was independent of prior firing since it occurred with subthreshold concentrations of ibotenate and when ibotenate firing had been blocked by DL-a-aminoadipate. 3. When administered electrophoretically for 5 min, muscimol, a potent GABA agonist, reduced neuronal excitability for prolonged periods and this effect was also prevented by bicuculline methochloride.4. The depression of neuronal excitability produced by GABA, taurine, isoguvacine or 3-aminopropane sulphonate, ejected for periods of 5-6 min, recovered rapidly.5. It is suggested that ibotenate is converted in vivo to muscimol or a related compound which has a prolonged, bicuculline-sensitive depressant action on the excitability of neurones.

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Section: Methodsmentioning

confidence: 99%

The excitation and depression of spinal neurones by ibotenic acid.

Curtis¹,

Lodge²,

McLennan³

1979

The Journal of Physiology

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“…From these points of view, our experimental conditions may, paradoxically, mimic synaptic release more closely than other studies have done, in that the GABA administrations were relatively short ( < 250 msec), were usually from a point source, and were close to the neurone under study. Indeed, uptake inhibition failed to affect not only responses to the fairly short GABA administrations in the present study, but also the even shorter synaptic inhibitions tested in the central nervous system (Curtis et al 1976;Lodge et al 1977). Other aspects must however be considered, in particular the fact that in the central nervous system most GABA uptake is probably by neuronal elements (see Iversen & Kelly, 1975); there also remains the possibility that the negative result obtained with tests on central inhibitions is due only to failure of the uptake inhibitors to reach synaptic regions (Curtis et al 1976).…”

Section: Discussionmentioning

confidence: 46%

“…GABA uptake has been postulated to be an important factor in terminating the action of GABA (see review by Iversen & Kelly, 1975). In electrophoretic tests in the central nervous system, inhibitors of GABA uptake do indeed potentiate the depressant action of GABA although they have no effect on synaptic transmissions thought to be mediated by GABA (Curtis, Game & Lodge, 1976; Lodge, Johnston, Curtis & Brand, 1977; see also Lodge, Curtis & Johnston, 1978). In the central nervous system, GABA is known to be taken up into both neuronal (principally nerve terminal) and glial elements (see Iversen & Kelly, 1975), but the relative importance of these two systems in affecting the characteristics of GABA responses has not yet been clarified.…”

Section: Introductionmentioning

confidence: 99%

Does glial uptake affect GABA responses? An intracellular study on rat dorsal root ganglion neurones in vitro

Desarménien

Feltz

Headley

1980

The Journal of Physiology

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SUMMARY1. Using single barrel pipettes, intracellular records were obtained from surface neurones of isolated rat dorsal root ganglia (DRG) impaled under microscopic vision.2. Responses to 7-aminobutyric acid (GABA) were elicited either by ionophoresis or by placing drops of concentrated GABA solutions directly into the flow of superfusing Ringer. Using this latter method it was estimated that the GABA concentration eliciting threshold (-1 mV) responses was 3-20 /LM.3. Short ( 1 see) ionophoretic or drop administrations of GABA elicited depolarizing responses associated with an increased membrane conductance. With longer applications the initial depolarization was not sustained but decayed to a lower plateau level (desensitization) associated with a minimal conductance change.4. Low chloride superfusions did not affect subsequent responses to GABA unless GABA was also administered during the low chloride superfusion, in which case responses declined markedly. This suggests that GABA caused appreciable chloride fluxes when it was administered regularly (e.g. for 1 see every minute).5. Glial GABA uptake was inhibited by adding 1 mM-fl-alanine or 0-25 mMchlorpromazine to the bicarbonate-Ringer superfusate or by substituting lithium for sodium in a Tris-Ringer superfusate. Uptake inhibition had no consistent effect on any of the parameters studied, namely membrane potential, input resistance, amplitude and time course of responses to GABA, and GABA desensitization.6. Muscimol and isoguvacine, which are probably not substrates for the glial GABA carrier, elicited responses with time course and desensitization characteristics indistinguishable from those of responses to GABA.7. GABA superfused at concentrations as low as 1 /tM could reduce responses to ionophoretic GABA, i.e. cause a desensitization of GABA receptors.8. It is concluded firstly that in DRG, glial uptake does not affect the amplitude or time course of responses to GABA when the neurone under study is close to the source of GABA; and secondly that desensitization can occur independently of GABA uptake.

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“…In the presence of lime, arecoline is hydrolyzed to arecaidine, which lacks the parasympathomimetic effects of arecoline (4) and exerts a sympathetic effect by inhibition of γ-aminobutyric acid (GABA) uptake (29). However, a later study suggested that arecaidine may not cross the blood-brain barrier and the central effects may involve transmitters other than GABA (30). The aromatic substances (e.g., eugenol, isoeugenol and hydroxychavicol) in the flowers or leaves of the Piper betle plant can stimulate the release of catecholamines from chromaffin cells in vitro (31), and circulating norepinephrine and epinephrine levels are elevated following betel nut chewing (32).…”

Section: Discussionmentioning

confidence: 99%