Topic
Hexobendine
About: Hexobendine is a research topic. Over the lifetime, 72 publications have been published within this topic receiving 2347 citations.
Papers published on a yearly basis
Papers
TL;DR: Adenosine is not the transmitter at this CA1 pyramidal cell synapse, but is apparently present in the extracellular compartment in sufficient concentrations to affect the synaptic physiology of this region, and this provides strong evidence in favour of the concept of a neuromodulatory role for adenosine in the central nervous system.
Abstract: 1 The effects of adenosine and various derivatives were examined in the in vitro hippocampal slice preparation from rat
2 The amplitudes of extracellularly recorded field potentials from the CA1 region were depressed by adenosine, and this effect could be antagonized by methylxanthines Because presynaptic field potentials were unaffected by adenosine, while the field epsp was depressed, adenosine would appear to act at a synaptic site to depress transmission
3 Adenosine deaminase, which breaks down adenosine to inosine, increased the amplitude of synaptic responses, while hexobendine, which blocks reuptake of adenosine, had a depressant effect This strongly suggests that the endogenous release of adenosine from the hippocampal slice preparation is sufficient to exert a tonic inhibitory influence on the amplitude of synaptic responses
4 Cyclic adenosine 3′,5′-monophosphate (cyclic AMP) and its dibutyryl derivative had depressant effects on the amplitude of field responses which were blocked by theophylline, suggesting that they are able to act at the extracellular adenosine receptor (-)-Isoprenaline (which raises tissue cyclic AMP levels), and the 8-p-chlorophenylthio derivative of cyclic AMP both increased the amplitude of population spike responses, and these effects were not blocked by theophylline, suggesting that the physiological effects of adenosine are not mediated via a cyclic AMP-dependent mechanism
5 Since adenosine is not the transmitter at this CA1 pyramidal cell synapse, but is apparently present in the extracellular compartment in sufficient concentrations to affect the synaptic physiology of this region, this provides strong evidence in favour of the concept of a neuromodulatory role for adenosine in the central nervous system
368 citations
TL;DR: The results are compatible with the hypothesis that the specific inhibition of uptake ofadenosine potentiates adenosine or amine-elicited accumulations of cyclic AMP by increasing the effective extracellular concentration of adenoine within the slice.
150 citations
TL;DR: The present findings suggest that there are at least two functional pools of adenosine in synaptosomes, and that the uptake may represent a facilitated diffusion process, which is saturable and temperature‐dependent.
Abstract: Adenosine, a putative inhibitory transmitter or modulator in the brain, is rapidly transported by rat cerebral cortical synaptosomes. The uptake may represent a facilitated diffusion process, which is saturable and temperature-dependent. In this study, the uptake process was very rapid, reaching completion within 60 s of incubation at 37 degrees C, and had an apparent Km value of 0.9 microM and a Vmax value of 5.26 pmol/mg protein/30 s. Over 70% of the adenosine taken up remained unchanged, whereas 14% was metabolized to inosine. Twelve percent of the adenosine was converted to nucleotides. Rapid uptake of adenosine into rat cerebral cortical synaptosomes was partially inhibited by replacing Na+ with choline chloride in the medium. Ca2+ ion is important for the uptake process, as inhibition of adenosine uptake occurs in the presence of either Co2+ or EGTA. Rapid uptake of adenosine is apparently mediated by a nucleoside carrier, a conclusion based on its inhibition by a variety of purine and pyrimidine nucleosides. Uptake was inhibited by dipyridamole, hexobendine, papaverine, flurazepam, and morphine. Over 60% of the adenosine taken up by the rapid uptake system (30 s) was released by depolarizing agents. In contrast, only 30% of the adenosine taken up during a 15-min incubation period was released under the same conditions. [3H]Adenosine was the predominant purine released in the presence or absence of depolarizing agents. The basal and KCl-evoked release mechanisms were found to be at least partially Ca2+-dependent, however, the release of adenosine by veratridine was increased in the presence of EGTA. This finding is in agreement with the reported Ca2+-independent release of ATP from brain synaptosomes. The present findings suggest that there are at least two functional pools of adenosine in synaptosomes. Adenosine taken up by different uptake systems may be destined for different uses (metabolism or release) in the neuron.
119 citations
TL;DR: It is concluded that adenosine was formed in the cytoplasm during catabolism of cellular ATP and was released via the dipyridamole-sensitive symmetric nucleoside transporter in neonatal-rat heart cell nucleotides in a concentration-dependent manner.
Abstract: The incorporation of [3H]adenosine (10 microM) into neonatal-rat heart cell nucleotides was inhibited in a concentration-dependent manner, such that 50% inhibition was obtained with 0.75 microM-dipyridamole, 0.26 microM-hexobendine or 0.22 microM-dilazep. Adenosine formation was accelerated 2.5-fold to 2.1 +/- 0.3 nmol/10(7) cells in 10 min when cells were incubated with a combination of 30 mM-2-deoxyglucose and 2 micrograms of oligomycin/ml. Of the newly formed adenosine, 6 +/- 2% was in the cells. Dipyridamole, hexobendine or dilazep (10 microM) increased the amount of adenosine in the cells and decreased that in the medium such that 45-50% of the newly formed adenosine was in the cells. Antibodies which inhibited ecto-5'-nucleotidase by 98.7 +/- 0.3% did not alter the rate of adenosine formation or its distribution between cells and medium. We conclude that adenosine was formed in the cytoplasm during catabolism of cellular ATP and was released via the dipyridamole-sensitive symmetric nucleoside transporter.
76 citations
TL;DR: It is concluded that adenosine exerts its effect on the heart rate by an extracellular site of action and may result from an inhibition of the uptake of the nucleoside into the tissues.
64 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2000 | 1 |
| 1993 | 1 |
| 1990 | 1 |
| 1989 | 1 |
| 1988 | 2 |
| 1987 | 1 |