Adenosine but not an adenine nucleotide mediates tonic purinergic inhibition, as well as inhibition by glutamate, of noradrenaline release in rabbit brain cortex slices.
A possible contribution of adenine nucleotides to the endogenous purinergic, A1-receptor-mediated inhibition of noradrenaline release was studied in rabbit occipito-parietal cortex slices. The slices were preincubated with [3H]-noradrenaline and then superfused and stimulated electrically, in most experiments by trains of 6 pulses/100 Hz. A few experiments were carried out in rat occipito-parietal cortex slices. The A1-purinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1-100 nmol/l) as well as the enzyme adenosine deaminase (0.1-10 U/ml) increased the electrically evoked overflow of tritiated compounds. The maximal increase was by about 85% for both DPCPX and adenosine deaminase. The increases obtained with maximally effective concentrations of DPCPX and adenosine deaminase were not additive. The alpha 1-adrenoceptor-selective agonist methoxamine (10 but not 1 mumol/l) reduced the evoked overflow. Its effect was antagonized by yohimbine 1 mumol/l but then not attenuated further by DPCPX 100 nmol/l. L-Glutamate (300 mumol/l-2.3 mmol/l) also reduced the evoked overflow of tritium. Its effect was not changed by yohimbine 1 mumol/l but greatly, and to the same extent, attenuated by DPCPX 100 nmol/l and adenosine deaminase 3 U/ml. Neither the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine nor omission of Mg++ changed the inhibition by glutamate. Glutamate did not alter the basal efflux of tritium from rabbit cortex slices under any experimental condition. In contrast, glutamate (100 mumol/l and 1 mmol/l) caused an immediate, marked and transient acceleration of tritium outflow from rat occipitoparietal cortex slices (medium without Mg++).(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmakologisches Institut, Freiburg, Federal Republic of Germany.
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von Kügelgen
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Späth
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Starke
D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D058914:Purinergic Antagonists; D011817:Rabbits; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology*
D005971:Glutamates; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D014970:Xanthines; D018698:Glutamic Acid; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000243:Adenosine Deaminase; D008729:Methoxamine; D000241:Adenosine; D009638:Norepinephrine