Characterization of adenosine receptors evoking excitation of mesenteric afferents in the rat

Kirkup, Anthony J.; Eastwood, C.; Grundy, David; Chessell, Iain P.; Humphrey, P.P.A.

doi:10.1038/sj.bjp.0702202

Cited by 29 publications

(29 citation statements)

References 32 publications

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“…This potential difference in the jugular nociceptive phenotype between the respiratory and gastrointestinal system may indicate that certain properties of vagal nociceptors are organ-or tissue-specific and warrants further investigation in the future. It has been previously reported that visceral spinal DRG afferent nerves are activated by adenosine (21). Our finding that the spinal DRG (i.e., neural crest-derived) afferent neurons are activated via the adenosine A 1 receptor is consistent with the previous reports in rat jejunum (6).…”

Section: Discussionsupporting

confidence: 94%

Adenosine-induced activation of esophageal nociceptors

Ren

Surdenikova

Brozmanová

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal nociceptors. Whole cell perforated patch-clamp recordings and single-cell RT-PCR analysis were performed on the primary afferent neurons retrogradely labeled from the esophagus in the guinea pig. Extracellular recordings were made from the isolated innervated esophagus. In patch-clamp studies, adenosine evoked activation (inward current) in a majority of putative nociceptive (capsaicin-sensitive) vagal nodose, vagal jugular, and spinal dorsal root ganglia (DRG) neurons innervating the esophagus. Single-cell RT-PCR analysis indicated that the majority of the putative nociceptive (transient receptor potential V1-positive) neurons innervating the esophagus express the adenosine receptors. The neural crest-derived (spinal DRG and vagal jugular) esophageal nociceptors expressed predominantly the adenosine A(1) receptor while the placodes-derived vagal nodose nociceptors expressed the adenosine A(1) and/or A(2A) receptors. Consistent with the studies in the cell bodies, adenosine evoked activation (overt action potential discharge) in esophageal nociceptive nerve terminals. Furthermore, the neural crest-derived jugular nociceptors were activated by the selective A(1) receptor agonist CCPA, and the placodes-derived nodose nociceptors were activated by CCPA and/or the selective adenosine A(2A) receptor CGS-21680. In contrast to esophageal nociceptors, adenosine failed to stimulate the vagal esophageal low-threshold (tension) mechanosensors. We conclude that adenosine selectively activates esophageal nociceptors. Our data indicate that the esophageal neural crest-derived nociceptors can be activated via the adenosine A(1) receptor while the placodes-derived esophageal nociceptors can be activated via A(1) and/or A(2A) receptors. Direct activation of esophageal nociceptors via adenosine receptors may contribute to the symptoms in esophageal diseases.

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Section: Discussionsupporting

confidence: 94%

Adenosine-induced activation of esophageal nociceptors

Ren

Surdenikova

Brozmanová

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…There is ample evidence that activation of spinal A 1 receptors results in antinociceptive effects in a wide range of animal models, including both acute nociceptive tests and models of neuropathic and inflammatory pain (see Dickenson et al, 2000;Sawynok, 1998). There is debate as to whether A 1 receptors on peripheral sensory nerves are pro-or antinociceptive, as inhibition of PGE 2 -induced nociception (Aley et al, 1995;Aley and Levine, 1997) and stimulation of sensory afferents (Dowd et al, 1998;Kirkup et al, 1998) has been reported after A 1 receptor activation. Overall, however, the antinociceptive effects of central A 1 receptors dominate and this is confirmed in A 1 receptor gene knockout mice, which have an enhanced response to nociceptive stimuli (Johansson et al, 2001).…”

Section: Adenosine and Its Role In Painmentioning

confidence: 99%

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Ferré

Diamond

Goldberg

et al. 2007

Progress in Neurobiology

128

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Adenosine A 2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A 2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A 2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A 2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A 2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A 2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A 1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A 2A receptors. A 2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A 1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A 2A receptor knockout mice suggest that A 2A receptor antagonists might have some therapeutic potential in pain states, in particular where high intensity stimuli are prevalent.

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“…Thus, whereas in rodents adenosine A 1 receptors are implicated in analgesia (see above), in humans pain-initiating actions of adenosine have been attributed to adenosine A 1 receptors (Pappagallo et al, 1993;Gaspardone et al, 1995). In addition, adenosine A 1 receptor agonists increase the firing of sensory afferent nerves (Dowd et al, 1998;Hong et al, 1998;Kirkup et al, 1998), and can cause neurogenic edema following local application in rodents Esquisatto et al, 2001). …”

Section: H Adenosinementioning

confidence: 99%