Effects of adenosine on norepinephrine and acetylcholine release from guinea pig right atrium: Role of A1-receptors

H. Nakatsuka, O. Nagano, F. F. Földes, H. Nagashima, E. Vízi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The effect of adenosine or its stable analogues (2-chloroadenosine, CADO: 5′-N-ethyl-carboxamidoadenosine, NECA; and N6-cyclopentyladenosine, CPA) and a non-selective A1 and A2-receptor antagonist, 8-phenyltheophylline (8-PT), or an A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), on the stimulation-evoked release of [3H]norepinephrine ([3H]NE) and [3H]ace-tylcholine ([3H]ACh) from the isolated guinea pig right atrium was investigated. Adenosine and its stable analogues (CADO, NECA and CPA) inhibited the stimulation-evoked release of [3H]NE in a concentration-dependent manner. The order of potencies was CPA > NECA > CADO > adenosine. CGS 21680 (30 nM), an A2a receptor agonist, failed to affect the release. The inhibitory effect of adenosine and CADO on [3H]NE release was competitively antagonized by 8-PT. DPCPX also prevented the effect of adenosine (Kd = 5.2 nM) and CADO (Kd = 3.3 nM). The Kd value of 8-PT was 0.40 μM for the antagonism of CADO and 0.51 μM for the antagonism of adenosine. When the negative feedback modulation of NE release was inhibited by idazoxan, the inhibitory effect of adenosine and CADO on [3H]NE release was more pronounced. Under this condition DPCPX (10 nM) prevented the inhibitory effect of CADO, indicating that A1-purinoceptors are involved in this action. The release of [3H]NE is tonically modulated by ACh released from the vagal nerve endings, as evidenced by the finding that 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), a M3-subtype selective muscarinic receptor antagonist, and atropine significantly enhanced the release of NE. Adenosine, its stable analogues (CADO and NECA), and 8-PT did not have any effect on the stimulation-evoked release of [3H]ACh. Even when the muscarinic autoinhibition was eliminated by atropine, adenosine and CADO did not have any effect on [3H]ACh release. Quinpirole, a selective D2-receptor agonist, and neuropeptide Y (NPY) failed to affect the release of ACh. However, atropine and 4-DAMP, a selective M3-receptor antagonist, significantly enhanced the stimulation-evoked release of [3H]ACh. These findings indicate that there are no presynaptic heteroceptors (adenosine, D21, and NPY) on the vagal nerve endings of the guinea pig right atrium. It is concluded that the sympathetic nerve endings of the guinea pig right atrium are equipped with A1-, subclass of purinoceptors and α2B and muscarinic (M3)-receptors. Cholinergic vagal nerve endings in the heart are only equipped with muscarinic autoreceptors. Therefore, adenosine liberated during hypoxia inhibits NE release from the cardiac sympathetic nerve and thereby protects against tachyarrhythmia caused by myocardial hypoxia. In contrast, adenosine does not inhibit the vagal innervation of the right atrium.

Original languageEnglish
Pages (from-to)345-353
Number of pages9
JournalNeurochemistry International
Volume27
Issue number4-5
DOIs
Publication statusPublished - 1995

Fingerprint

Heart Atria
Adenosine
Acetylcholine
Norepinephrine
Guinea Pigs
Adenosine-5'-(N-ethylcarboxamide)
Nerve Endings
Atropine
Cholinergic Agents
Purinergic Receptors
2-Chloroadenosine
Muscarinic M3 Receptors
Neuropeptide Y Receptors
Idazoxan
Quinpirole
Autoreceptors
Muscarinic Antagonists
Neuropeptide Y
Muscarinic Receptors
varespladib methyl

ASJC Scopus subject areas

  • Cell Biology
  • Cellular and Molecular Neuroscience
  • Molecular Biology

Cite this

Effects of adenosine on norepinephrine and acetylcholine release from guinea pig right atrium : Role of A1-receptors. / Nakatsuka, H.; Nagano, O.; Földes, F. F.; Nagashima, H.; Vízi, E.

In: Neurochemistry International, Vol. 27, No. 4-5, 1995, p. 345-353.

Research output: Contribution to journalArticle

Nakatsuka, H. ; Nagano, O. ; Földes, F. F. ; Nagashima, H. ; Vízi, E. / Effects of adenosine on norepinephrine and acetylcholine release from guinea pig right atrium : Role of A1-receptors. In: Neurochemistry International. 1995 ; Vol. 27, No. 4-5. pp. 345-353.
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T2 - Role of A1-receptors

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AU - Nagano, O.

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AU - Nagashima, H.

AU - Vízi, E.

PY - 1995

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N2 - The effect of adenosine or its stable analogues (2-chloroadenosine, CADO: 5′-N-ethyl-carboxamidoadenosine, NECA; and N6-cyclopentyladenosine, CPA) and a non-selective A1 and A2-receptor antagonist, 8-phenyltheophylline (8-PT), or an A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), on the stimulation-evoked release of [3H]norepinephrine ([3H]NE) and [3H]ace-tylcholine ([3H]ACh) from the isolated guinea pig right atrium was investigated. Adenosine and its stable analogues (CADO, NECA and CPA) inhibited the stimulation-evoked release of [3H]NE in a concentration-dependent manner. The order of potencies was CPA > NECA > CADO > adenosine. CGS 21680 (30 nM), an A2a receptor agonist, failed to affect the release. The inhibitory effect of adenosine and CADO on [3H]NE release was competitively antagonized by 8-PT. DPCPX also prevented the effect of adenosine (Kd = 5.2 nM) and CADO (Kd = 3.3 nM). The Kd value of 8-PT was 0.40 μM for the antagonism of CADO and 0.51 μM for the antagonism of adenosine. When the negative feedback modulation of NE release was inhibited by idazoxan, the inhibitory effect of adenosine and CADO on [3H]NE release was more pronounced. Under this condition DPCPX (10 nM) prevented the inhibitory effect of CADO, indicating that A1-purinoceptors are involved in this action. The release of [3H]NE is tonically modulated by ACh released from the vagal nerve endings, as evidenced by the finding that 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), a M3-subtype selective muscarinic receptor antagonist, and atropine significantly enhanced the release of NE. Adenosine, its stable analogues (CADO and NECA), and 8-PT did not have any effect on the stimulation-evoked release of [3H]ACh. Even when the muscarinic autoinhibition was eliminated by atropine, adenosine and CADO did not have any effect on [3H]ACh release. Quinpirole, a selective D2-receptor agonist, and neuropeptide Y (NPY) failed to affect the release of ACh. However, atropine and 4-DAMP, a selective M3-receptor antagonist, significantly enhanced the stimulation-evoked release of [3H]ACh. These findings indicate that there are no presynaptic heteroceptors (adenosine, D21, and NPY) on the vagal nerve endings of the guinea pig right atrium. It is concluded that the sympathetic nerve endings of the guinea pig right atrium are equipped with A1-, subclass of purinoceptors and α2B and muscarinic (M3)-receptors. Cholinergic vagal nerve endings in the heart are only equipped with muscarinic autoreceptors. Therefore, adenosine liberated during hypoxia inhibits NE release from the cardiac sympathetic nerve and thereby protects against tachyarrhythmia caused by myocardial hypoxia. In contrast, adenosine does not inhibit the vagal innervation of the right atrium.

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