Summary
Effects of adenosine and nucleotides on the release of previously stored [3H]-noradrenaline were studied in rabbit brain cortex slices. The slices were stimulated twice, in most experiments by 6 electrical field pulses delivered at 100 Hz.
Adenosine and the nucleotides AMP, ADP, ATP, AMPS, ADPβS, ATPyS, β,γ-imido-ATP and β,γ-methyl-ene-ATP all reduced the evoked overflow of tritiated compounds. For purines for which concentration-response curves were determined, the order of potency was adenosine > ATP ≈ ATPyS β,γ-imido-ATP ≈ ADP > β,γ-methylene-ATP. AMP 30 Etmol/l and AMPS 30 μmol/l were approximately equieffective with 30 μmol/l of adenosine and ATPγS, and ADPβS, 30 μmol/l was approximately equieffective with 30 μmol/l of ADP. α,β-Methylene-ADP, 2-methylthio-ATP, UTP and GTPγS did not change the evoked overflow of tritium. α,β-Methylene-ATP caused an increase; however, the increase was small and became significant only after 59 min of exposure to α,β-methylene-ATP or when the slices were stimulated by 30 pulses, 10 H2. Neither adenosine deaminase (100 U/l) nor the blocker of 5′-nucleotidase, α,β-methylene-ADP (10 μmol/l), attenuated the inhibition caused by ATP, ATPyS and β,γ-methylene-ATP, despite the fact that adenosine deaminase abolished the effect of adenosine. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nmol/l) shifted the concentration-response curves of adenosine, ATPyS, β,γ-imido-ATP and β,γ-methylene-ATP to the right by very similar degrees. 8(p-Sulphophenyl)-theophylline (30 and 300 μmol/l) also markedly antagonized the inhibition produced by ATPγS. α,β-Methylene-ATP (10 and 30 μmol/l) and suramin (100 gmol/l) did not modify the effects of adenosine, ATPγS and β,γ-methylene-ATP.
It is concluded that nucleotides themselves can inhibit the release of noradrenaline in the rabbit brain cortex. The nucleotides and adenosine seem to act at the same site, i.e., the A1 subtype of the P1-purinoceptor. The results support the notion that metabolically stable, phosphate chain-modified nucleotides such as ATPγS, β,γ-imido-ATP and β,γ-methylene-ATP can be potent P1 agonists. No evidence was found for presynaptic P2X-, P2Y- or P3-purinoceptors.
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von Kügelgen, I., Späth, L. & Starke, K. Stable adenine nucleotides inhibit [3H]-noradrenaline release in rabbit brain cortex slices by direct action at presynaptic adenosine A1-receptors. Naunyn-Schmiedeberg's Arch Pharmacol 346, 187–196 (1992). https://doi.org/10.1007/BF00165300
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DOI: https://doi.org/10.1007/BF00165300