Interactions between calcium channel compounds and adenosine systems in brain of rat

Morgan, Page W.; Tamborska, E; Patel, Jitendra; Pj, Marangos

doi:10.1016/0028-3908(87)90119-5

Cited by 26 publications

(23 citation statements)

References 18 publications

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“…No change in field EPSP size was seen during ethanol withdrawal in the present study. An increase in calcium channel conductance might be expected to decrease GABAA-mediated inhibition by altering the affinity of the GABA receptor for GABA (Inoue, Oomura, Yakushiji & Akaike, 1986), but our measurements of fast IPSP amplitude in hippocampal slices, recorded under the same conditions as the present results, showed that these responses were not decreased at any time during ethanol withdrawal, and were in fact significantly increased at 2 h into the withdrawal period (Whittington et al 1992 (Morgan, Tamborska, Patel & Marangos, 1987). A decrease in presynaptic inhibition mediated by adenosine has been shown to decrease paired-pulse potentiation in the rat hippocampus (Dunwiddie & Haas, 1985).…”

Section: Intracellular Recordingsmentioning

confidence: 46%

Changes in voltage‐operated calcium channels modify ethanol withdrawal hyperexcitability in mouse hippocampal slices

Whittington¹,

Little²

1993

Experimental Physiology

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SUMMARYMeasurements of hippocampal excitability were made from area CAl of isolated mouse hippocampal slices, prepared after chronic ethanol treatment in vivo, and the effects of the stereoisomers of the dihydropyridine Bay K 8644, that act at calcium channels, were investigated. The decrease in the threshold stimulation required to produce a single population spike, the leftward shift in the population spike input-output curves, and the increase in population spike amplitude, that were seen during ethanol withdrawal, were all increased by the (-) isomer of Bay K 8644. This isomer has been shown to increase opening of calcium channels. These effects of ethanol withdrawal were decreased by the (+) isomer of Bay K 8644, that is a calcium channel blocker. In contrast, the increase in paired-pulse potentiation of the population spike, seen during the initial phase of ethanol withdrawal, was significantly decreased by both isomers of Bay K 8644. After the chronic ethanol treatment, single orthodromic stimuli produced epileptiform field potentials, consisting of two independent phases, a short latency series of multiple population spikes, superimposed upon the initial observed EPSP, and a longer latency train of spikes, occurring on a second EPSP, temporally distinct from the first. The (-) isomer of Bay K 8644 increased both these phases of epileptiform activity during ethanol withdrawal in a dose-dependent manner, while (+)-Bay K 8644 reduced the initial phase of multiple spiking and abolished the later phase. In slices from control animals, the higher concentration of (-)-Bay K 8644 (2 /sM), but not the lower concentration (500 nM) decreased the stimulation required to produce multiple population spikes. Neither produced the long latency epileptiform activity. The (+) isomer of Bay K 8644 had no effect on control recordings. Lesioning the Schaffer collateral-commissural fibre pathway, or removing area CA3, in slices from ethanol-treated animals, abolished the later phase of epileptiform activity without affecting the initial multiple spiking. Intracellular recordings from area CAl showed both the short latency and the longer latency epileptiform activities in slices from ethanol-treated mice and in control hippocampal slices after application of the (-) isomer of Bay K 8644, but these patterns of activity were not seen in control slices in the absence of Bay K 8644. Spontaneous activity during ethanol withdrawal was seen in intracellular recordings, but such activity was not seen in the field potential recordings. It is suggested that withdrawal from chronic ethanol treatment produced hyperexcitability in both area CAl and area CA3 of the isolated hippocampal slice, and that the epileptiform activity in area CA3 is effectively transmitted to area CAl. The effects of the isomers of Bay K 8644 suggested that this epileptiform activity was mediated, in part, by activity of dihydropyridinesensitive calcium channels.

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Section: Intracellular Recordingsmentioning

confidence: 46%

Changes in voltage‐operated calcium channels modify ethanol withdrawal hyperexcitability in mouse hippocampal slices

Whittington¹,

Little²

1993

Experimental Physiology

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“…For example, nifedipine is known to interact with the adenosine system by acting as an antagonist to its receptor and͞or interfering with its uptake system at a micromolar potency (18). It is possible that the massive increase in mEPSC frequency induced by nifedipine is due to disinhibition of inhibitory modulation by adenosine (19).…”

Section: Resultsmentioning

confidence: 99%

Nifedipine facilitates neurotransmitter release independently of calcium channels

Hirasawa

Pittman²

2003

Proc. Natl. Acad. Sci. U.S.A.

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Nifedipine, a drug used for treatment of hypertension and angina, exerts its effect by calcium channel blockade and nitric oxide production. We report here a previously uncharacterized action of nifedipine on central synaptic transmission that may partially explain its side effects. Nifedipine causes a long-lasting facilitation of tetrodotoxin-insensitive spontaneous glutamate release. This effect is independent of its L-type calcium channel blocking effect, and is not mimicked by other dihydropyridines such as nimodipine, nicardipine, or Bay K 8644. The effect was dose dependent, with EC 50 of 7.8 M, with the lowest effective dose being 100 nM, a clinically relevant dose. At 10 M, the increase is 14.7-fold. This effect is largely calcium-independent, because Cd 2؉ , thapsigargin, or BAPTA-AM [1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid-acetoxymethyl ester] did not inhibit the nifedipine effect. Thus, nifedipine seems to act on the release process downstream of calcium entry or release. Protein kinases A or C do not mediate its effect, because it is not blocked by inhibitors of these kinases. Our finding indicates that nifedipine may be a useful tool as a secretagogue to directly target the release process, but raises caution for its use as an L-type calcium channel blocker. N ifedipine has been a commonly prescribed compound for treatment of angina and hypertension. Its clinical effect is attributed to its blocking action on L-type calcium channels or release of nitric oxide (NO) from the vascular endothelium, which will result in relaxation or prevention of cardiac or vascular smooth muscle contraction. Compared with other dihydropyridines (DHPs), nifedipine has been reported to have relatively high incidence of neurologic adverse reactions, such as dizziness (4.1-27%) and nervousness (Ͼ7.0%) (information obtained from www.drugdigest.org͞DD͞SE͞DisplayDrug͞1,3997,488,00. html?DVHNameϭNifedipine). Nifedipine can easily cross the brain-blood barrier (1); thus, it may have a direct effect in the brain. The present report introduces a previously uncharacterized action of nifedipine on synaptic transmission in the central nervous system. Nifedipine induces a profound increase in spontaneous glutamate release in a calcium-independent manner. This effect was unique to nifedipine and could not be mimicked by other DHPs; thus, its action is not through blockade of L-type calcium channels. Such synaptic activation in the central nervous system may underlie some of its adverse neurologic reactions.Spontaneous, action potential-independent transmitter release occurs when a synaptic vesicle fuses spontaneously to the presynaptic plasma membrane and releases its content. It is not yet clear what may be the role of spontaneous release for the function of the nervous system. Recent studies indicate that spontaneously released glutamate acts to maintain the postsynaptic dendritic structure (2) and to induce clustering of AMPA (␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors on the postsynaptic membran...

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“…The relevance of these changes is uncertain. Although only NFD is known to inhibit CHA binding in vitro (Morgan et al, 1987), both dihydropyridines in the present study were seen to affect K, in the cerebellum. Previous work would predict a change in B,,, rather than K, (Marangos et ai., 1985).…”

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confidence: 47%

Lack of Major Effects on Mouse Brain Adenosine A₁ Receptors of Oral Carbamazepine and Calcium Antagonists

et al. 1991

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Interaction with adenosine A1 receptors is a possible contributory mechanism to the anticonvulsant effects of carbamazepine (CBZ) and the dihydropyridine calcium antagonists. We measured the binding of [3H]cyclohexyladenosine to adenosine A1 receptors in mouse brain stem, cerebellum, and cortex after oral administration of nifedipine, nimodipine (NMD), and CBZ for 7 days and compared the results with binding in control mice. Equilibrium dissociation constant (Kd) and receptor numbers (Bmax) were calculated using Scatchard and saturation isotherm analyses. Mean Kds (SEM) in control brain stem, cerebellum, and cortex were 2.09 (0.31), 2.39 (0.2), and 3.12 (0.28) nM, respectively. Results of Bmax for the same areas were 188 (26), 280 (24), and 449 (54) fmol/mg protein. Nifedipine (p less than 0.005) and NMD (p less than 0.02) raised the Kd of A1 receptors only in the cerebellum, and CBZ increased cerebellar Bmax (p less than 0.05). These minor effects on A1 receptors in CF1 mice, when given in doses previously shown to have anticonvulsant properties in these animals, do not suggest that alteration in A1 receptor activity is an important mechanism for the anticonvulsant effects of these drugs.

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Interactions between calcium channel compounds and adenosine systems in brain of rat

Cited by 26 publications

References 18 publications

Changes in voltage‐operated calcium channels modify ethanol withdrawal hyperexcitability in mouse hippocampal slices

Changes in voltage‐operated calcium channels modify ethanol withdrawal hyperexcitability in mouse hippocampal slices

Nifedipine facilitates neurotransmitter release independently of calcium channels

Lack of Major Effects on Mouse Brain Adenosine A₁ Receptors of Oral Carbamazepine and Calcium Antagonists

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Interactions between calcium channel compounds and adenosine systems in brain of rat

Cited by 26 publications

References 18 publications

Changes in voltage‐operated calcium channels modify ethanol withdrawal hyperexcitability in mouse hippocampal slices

Changes in voltage‐operated calcium channels modify ethanol withdrawal hyperexcitability in mouse hippocampal slices

Nifedipine facilitates neurotransmitter release independently of calcium channels

Lack of Major Effects on Mouse Brain Adenosine A1 Receptors of Oral Carbamazepine and Calcium Antagonists

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Product

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Lack of Major Effects on Mouse Brain Adenosine A₁ Receptors of Oral Carbamazepine and Calcium Antagonists