Direct evidence for ATP release from non-adrenergic, non-cholinergic (“purinergic”) nerves in the guinea-pig taenia coli and bladder

Burnstock, Geoffrey; Cocks, T. M.; Kasakov, L.; Wong, H.

doi:10.1016/0014-2999(78)90070-5

Cited by 202 publications

(81 citation statements)

References 10 publications

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“…The identity of these neurotransmitters has been extensively investigated. First ATP and then VIP, were regarded as putative neurotransmitters in the gut (Burnstock et al, 1978;Manzini et al, 1986;Grider & Makhlouf, 1988). More recently, nitric oxide (NO) has been viewed as the main NANC inhibitory neurotransmitter in the gastrointestinal tract of many species (Boeckxstaens et al, 1991;Burleigh, 1992;Suthamnatpong et al, 1994;Serio et al, 1995;Takeuchi et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Plujà

Fernández

Jiménez

1999

British J Pharmacology

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1 The rat colonic circular muscle displays cyclic episodes of myenteric potential oscillations (MPOs), each of them associated with a spontaneous contraction. Nifedipine 1 mM abolished both MPOs and their associated contractions. TTX (1 mM) increased the amplitude and frequency of spontaneous contractions. 2 Electrical ®eld stimulation (EFS) induced a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (IJP), with two phases: an initial fast hyperpolarization (characterized by IJP amplitude) and a sustained hyperpolarization (characterized by IJP duration). 3 Sodium nitroprusside (10 mM) hyperpolarized and abolished spontaneous contractions even in presence of TTX or 1 mM apamin. ATP (100 mM) also hyperpolarized and abolished spontaneous contractions but its e ects were decreased by TTX and abolished by apamin. 4 Suramin (100 mM) or apamin reduced the amplitude of the IJPs, but did not a ect their duration. Incubation with L-NOARG (1 mM) reduced the duration but not the amplitude of the IJPs. In presence of L-NOARG plus suramin or L-NOARG plus apamin, both duration and amplitude of the IJPs were reduced but a residual IJP could still be recorded. 5 We conclude that the mechanical and electrical cyclic activity of the rat colonic circular muscle is modulated but not originated by the enteric nervous system and involves L-type calcium channel activity. EFS induces release of NANC inhibitory neurotransmitters which hyperpolarize and relax smooth muscle cells. Both ATP and NO are involved in IJP generation: ATP is responsible for the ®rst phase of the IJPs involving activation of apamin-sensitive potassium channels, whereas NO initiates the second phase which is independent of the activation of such channels.

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Section: Introductionmentioning

confidence: 99%

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Plujà

Fernández

Jiménez

1999

British J Pharmacology

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“…Further, the role of ATP as a neurotransmitter of the 'purinergic' nerves has been emphasized in guinea-pig urinary bladder by the demonstration of endogenous ATP release on transmural nerve stimulation as well as by the presence of ATP containing nerves shown by fluorescence histochemistry (Burnstock et al, 1978). Purines, particularly adenosine, are known to modulate the release of classical neurotransmitters like ACh, noradrenaline and dopamine in both central and peripheral nervous systems (Snyder, 1985).…”

Section: Introductionmentioning

confidence: 99%

Adenosine‐ and α,β‐methylene ATP‐induced differential inhibition of cholinergic and non‐cholinergic neurogenic responses in rat urinary bladder

Raviprakash

Mishra

1991

British J Pharmacology

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1 The effects of adenosine and a,4-methylene adenosine triphosphate (a,4-Me ATP) on single pulseinduced neurogenic responses and contractions caused by exogenously applied acetylcholine (ACh) and adenosine triphosphate (ATP) were examined in rat urinary bladder. 2 Application of single pulse stimulation (1 ms; 80V) evoked a biphasic contractile response (abolished by tetrodotoxin, 0.5 x 1O-7M) consisting of a fast (time to peak: 1.02 + 0.07 s) and a slow component 4 Adenosine (10-8M to 1O-4M) caused dose-related differential inhibition of the fast (IC5o, 1.04 + 0.25 x 10-SM) and slow (IC50, 2.18 + 0.69 x 10-6M) components, thereby further supporting two modes of neurotransmission in bladder. 5 Theophylline (10-4M) antagonized the inhibitory effects of adenosine on the non-cholinergic component, thereby implicating the participation of P1-purinoceptors in neuromodulation. In contrast, theophylline at this concentration enhanced the adenosine-induced inhibition of the cholinergic component. 6 The magnitude of ATP (10-4M)-and ACh (10-8M)-induced contractions were almost identical to those of the fast and slow components of the neurogenic response, respectively. Comparable reduction of ATP (30.2 + 3.4%) and ACh (100%) contractions to those of fast (44.2 + 6.5%) and slow (88.2 + 5.5%) components suggests the involvement of a postjunctional mechanism in adenosine-induced differential inhibition of neurogenic responses. 7 The lack of effect of erythro-6-amino-9-(2-hydroxy-3-nonyl) adenosine hydrochloride (10-6M) and dipyridamole (10-6M) suggests that endogenous adenosine plays little part in modulation of single pulseinduced neurogenic response. 8 The results of the present study suggest that fast and slow components of neurogenic response are mediated through ATP and ACh, respectively, possibly co-released from the same neurone in the rat bladder.

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“…It has a 240 amino acid longer intracellular C-terminus than other P2X receptors. P2X 7 , cloned from rat macrophages and brain, is the cytolytic P2 receptor previously described in mast cells, fibroblasts and macrophages. Receptor distribution is generally limited to hemopoietic bone marrow cells including granulocytes, monocytes, macrophages, B-lymphocytes, erythrocytes and erythroleukemia cells.…”

Section: The Platelet P2x 1 Receptor For Atp the Family Of P2x Receptorsmentioning

confidence: 99%

The Platelet ATP and ADP Receptors

Oury

Tóth-Zsámboki

Vermylen

et al. 2006

CPD

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Adenine nucleotides, ADP and ATP, are coreleased from dense granules during platelet activation, as well as from endothelial cells and damaged red blood cells following vascular injury. Through autocrine and paracrine mechanisms, these extracellular signaling molecules interact with the platelet P2 receptors to amplify ongoing platelet activation. Two receptors for ADP, the G q -protein-coupled P2Y 1 and G i -protein-coupled P2Y 12 and one receptor for ATP, the P2X 1 ion channel, have been identified on platelets. Due to distinct pharmacological properties and differential regulation, the P2Y and P2X receptors essentially operate on different scales of time and distance and trigger selective intracellular signaling cascades. Recent advances in the understanding of the P2Y receptor physiology have reinforced the concept of these receptors as useful targets for antithrombotic therapy. The function of P2X 1 in platelet activation only recently started to be unraveled. This review focuses on recent findings on the physiology of these platelet ADP and ATP receptors, their distinct downstream intracellular signaling pathways as well as on the available agonists, antagonists and inhibitors that allow their pharmacological discrimination.Key Words: Hemostasis, thrombosis, adenine nucleotides, P2Y 1 , P2Y 12 , P2X 1 , antithrombotic therapy. HISTORY AND CLASSIFICATION OF PURINERGIC RECEPTORSThe first report about the potent actions of an adenine compound, AMP, extracted from heart muscle, was published by Drury and Szent-Györgyi in 1929. Initial investigations focused on effects of adenosine and ATP on the heart and vasculature, or concerned the effects of purines on platelets [1] and on mast cells. Further insights into the physiological role of extracellular purines and pyrimidines were provided via the study of their biological sources [2]. In this respect, the detection of nucleotide release from the heart during hypoxia [3] or from skeletal muscle during contraction indicated that secretion of purine compounds might be coupled to metabolic demand to regulate local blood flow. ATP release from sensory nerves suggested that adenine nucleotides play a role as neurotransmitter or neuromodulator in the central and peripheral nervous system [4].These early publications established that purinergic nucleotides act as extracellular signaling molecules [5]. Nucleotides are now documented to contribute to a diverse range of physiological responses such as smooth muscle contraction, neurotransmission, exocrine and endocrine secretion, immune response, inflammation, platelet aggregation, male reproduction, nociception and modulation of cardiac function [6].Purines and pyrimidines mediate their effects by interacting with distinct cell-surface receptors. Purinergic receptors were first formally recognized by Burnstock in 1978 [7]. They were divided into two classes: at P1-purinoceptors adenosine is the principal natural ligand, while P2-purinoceptors recognize both purine and pyrimidine nucleotides Based on an increasin...

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Direct evidence for ATP release from non-adrenergic, non-cholinergic (“purinergic”) nerves in the guinea-pig taenia coli and bladder

Cited by 202 publications

References 10 publications

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

Adenosine‐ and α,β‐methylene ATP‐induced differential inhibition of cholinergic and non‐cholinergic neurogenic responses in rat urinary bladder

The Platelet ATP and ADP Receptors

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