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P 2 ‐purinoceptor‐mediated inhibition of noradrenaline release in rat atria
Author(s) -
Kügelgen Ivar,
Stoffel Daniel,
Starke Klaus
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15870.x
Subject(s) - chemistry , pharmacology , norepinephrine , neuroscience , medicine , biology , dopamine
1 We looked for P 2 ‐purinoceptors modulating noradrenaline release in rat heart atria. Segments of the atria were preincubated with [ 3 H]‐noradrenaline and then superfused with medium containing desipramine (1 μ m ) and yohimbine (1 μ m ) and stimulated electrically, by 30 pulses/I Hz unless stated otherwise. 2 The adenosine A l ‐receptor agonist, N 6 ‐cyclopentyl‐adenosine (CPA; EC 50 9.7 nM) and the nucleotides, ATP (EC 50 6.6 μ m ) and adenosine‐5′‐O‐(3‐thiotriphosphate) (ATPγS; EC 50 4.8 μ m ), decreased the evoked overflow of tritium. The adenosine A 2a ‐agonist, 2‐ p ‐(2‐carbonylethyl)‐phenethylamino‐5′‐N‐ethylcarboxamido‐adenosine (CGS‐21680; 0.03‐0.3 μ m ) and the P 2X ‐purinoceptor agonist β,γ,‐methylene‐ l ‐ATP (30 μ m ) caused no change. 3 The concentration‐response curve of CPA was shifted to the right by the adenosine A l ‐receptor antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX; 3 nM; apparent pK B value 9.7) but hardly affected by the P 2 ‐purinoceptor antagonist, cibacron blue 3GA (30 μ m ). In contrast, the concentration‐response curves of ATP and ATPγS were shifted to the right by DPCPX (3 nM; apparent p K B values 9.3 and 9.4, respectively) as well as by cibacron blue 3GA (30 μ m ; apparent p K B values 5.0 and 5.1, respectively). Combined administration of DPCPX and cibacron blue 3GA caused a much greater shift of the concentration‐response curve of ATP than either antagonist alone. The concentration‐response curve of ATP was not changed by indomethacin, atropine or the 5′‐nucleotidase blocker α,β‐methylene‐ADP. 4 Cibacron blue 3GA (30 μ m ) increased the evoked overflow of tritium by about 70%. The increase was smaller when the slices were stimulated by 9 pulses/100 Hz instead of 30 pulses/I Hz. 5 The results indicate that the postganglionic sympathetic axons in rat atria possess P 2 ‐purinoceptors in addition to the known adenosine A l ‐receptor. Both mediate inhibition of noradrenaline release. Some adenine nucleotides such as ATP and ATPγS act at both receptors. The presynaptic P 2 ‐purinoceptor seems to be activated by an endogenous ligand, presumably ATP, under the condition of these experiments. This is the first evidence for presynaptic P 2 ‐purinoceptors at cardiac postganglionic sympathetic axons.