Central adenosine A<sub>1</sub> receptors inhibit cough <i>via</i> suppression of excitatory glutamatergic and tachykininergic neurotransmission

El-Hashim, Ahmed Z.; Mathews, S. V. rghese; Al‐Shamlan, Fajer

doi:10.1111/bph.14360

Cited by 4 publications

(4 citation statements)

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“…Next, we measured airway responsiveness using wholeb o dy pl e t h y s m og r ap h y w i t h m e t h a c ho l i n e a s a bronchoprovocant as previously described [24,26]. While the use of whole body plethysmography is controversial, it continues to be used to assess airway responsiveness [24, [26][27][28][29]. We measured effect of limonene on airway responsiveness as enhanced pause (Penh) using increasing doses of methacholine and nonselective adenosine analog NECA in A 2A KO and WT mice.…”

Section: Discussionmentioning

confidence: 99%

Limonene-induced activation of A2A adenosine receptors reduces airway inflammation and reactivity in a mouse model of asthma

Patel

Narke

Kurade

et al. 2020

Purinergic Signalling

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Animal models of asthma have shown that limonene, a naturally occurring terpene in citrus fruits, can reduce inflammation and airway reactivity. However, the mechanism of these effects is unknown. We first performed computational and molecular docking analyses that showed limonene could bind to both A 2A and A 2B receptors. The pharmacological studies were carried out with A 2A adenosine receptor knock-out (A 2A KO) and wild-type (WT) mice using ovalbumin (OVA) to generate the asthma phenotype. We investigated the effects of limonene on lung inflammation and airway responsiveness to methacholine (MCh) and NECA (nonselective adenosine analog) by administering limonene as an inhalation prior to OVA aerosol challenges in one group of allergic mice for both WT and KO. In whole-body plethysmography studies, we observed that airway responsiveness to MCh in WT SEN group was significantly lowered upon limonene treatment but no effect was observed in A 2A KO. Limonene also attenuated NECA-induced airway responsiveness in WT allergic mice with no effect being observed in A 2A KO groups. Differential BAL analysis showed that limonene reduced levels of eosinophils in allergic WT mice but not in A 2A KO. However, limonene reduced neutrophils in sensitized A 2A KO mice, suggesting that it may activate A 2B receptors as well. These data indicate that limonene-induced reduction in airway inflammation and airway reactivity occurs mainly via activation of A 2A AR but A 2B receptors may also play a supporting role.

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Section: Discussionmentioning

confidence: 99%

Limonene-induced activation of A2A adenosine receptors reduces airway inflammation and reactivity in a mouse model of asthma

Patel

Narke

Kurade

et al. 2020

Purinergic Signalling

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“…At the level of the brainstem, the nucleus tractus solitarius associated with the cough center is not only regulated by the higher cortical center; it is also closely related to other functional centers of the body ( Widdicombe et al, 2011 ). The paraventricular nucleus, a center for regulating body temperature, receives afferent terminations from the nucleus tractus solitarius, emits efferent projections to the cough center, and transmits synaptic signals through SP and its receptor, neurokinin 1 ( El-Hashim et al, 2018 ). Afferent impulses from the nose, mouth, throat, esophagus, and skin can converge in the cough center, and modify cough sensitivity by affecting the interactions among different types of receptors and the functional relationships between various centers ( Widdicombe et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

et al. 2020

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Cough exacerbation in cold environments is a characteristic feature of patients with chronic cough. There is consensus that inhalation of cold air stimulates cough receptors but this idea is not consistent with the fact that cold air is usually unable to directly enter the lower airway. To elucidate the effects of cold environments and transient receptor potential ankyrin 1 (TRPA1) on cough, we compared cough reactivity, airway inflammation, and TRPA1 expression in guinea pigs with chronic cough induced by the repeated inhalation of citric acid for 15 days. The guinea pigs were exposed to cold environments for three consecutive days from day 13 to 15. Repeated inhalation of citric acid increased cough reactivity to inhaled cinnamaldehyde. We found that exposure to cold environments further aggravated cough hyperreactivity in guinea pigs with chronic cough, but not in normal guinea pigs. Cough hyperreactivity was promoted when the whole body and trunk-limbs, but not the heads, of the guinea pigs were exposed to cold environments, and abolished by pretreating the skin through immersion in the TRPA1 antagonist, HC-030031. Substance P levels in bronchoalveolar lavage fluid, and TRPA1 expression in the trachea and skin, were increased in guinea pigs when the whole body and trunk-limbs, rather than the head, were exposed to cold environments. However, this trend was also abolished by pretreatment of the skin via immersion in HC-030031. Similar changes in TRPA1 expression were also detected in the sensory fibers of the trachea and skin, as identified by immunofluorescence and laser-scanning confocal microscopy analysis. These results suggest that exaggerated cough hyperreactivity induced by cold environments may be related to activation of the cold-sensing TRPA1 signaling pathway in the skin, rather than the inhalation of cold air.

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“…A 1 AR is G i -coupled and its activation inhibits AC activity (inhibition of cAMP production), which leads to hyperpolarization by increasing potassium conductance, blocks transient calcium channel opening, and stimulates PLC, inducing an increase in inositol 1,4,5-triphosphate (IP 3 ) and intracellular Ca 2+ levels and stimulation of calcium-binding proteins such as protein kinase C (PKC) [ 128 ]. Furthermore, A 1 AR presynaptically inhibits primary sensory neuron transmission onto dorsal spinal neurons by blocking neurotransmitter release [ 126 , 129 ]. Moreover, when primary sensory afferent neurons depolarize, afferent nerve terminals release glutamate and SP, but also adenosine, in the dorsal spinal cord [ 129 ].…”

Section: Involvement Of Purinergic Signaling In Endometriosis-assomentioning

confidence: 99%

“…Furthermore, A 1 AR presynaptically inhibits primary sensory neuron transmission onto dorsal spinal neurons by blocking neurotransmitter release [ 126 , 129 ]. Moreover, when primary sensory afferent neurons depolarize, afferent nerve terminals release glutamate and SP, but also adenosine, in the dorsal spinal cord [ 129 ]. In this situation, adenosine can act as a negative modulator by activating A 1 AR at postsynaptic sites.…”

Section: Involvement Of Purinergic Signaling In Endometriosis-assomentioning

confidence: 99%

Purinergic Signaling in Endometriosis-Associated Pain

Trapero

Martı́n-Satué

2020

IJMS

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Endometriosis is an estrogen-dependent gynecological disease, with an associated chronic inflammatory component, characterized by the presence of endometrial tissue outside the uterine cavity. Its predominant symptom is pain, a condition notably altering the quality of life of women with the disease. This review is intended to exhaustively gather current knowledge on purinergic signaling in endometriosis-associated pain. Altered extracellular ATP hydrolysis, due to changes in ectonucleotidase activity, has been reported in endometriosis; the resulting accumulation of ATP in the endometriotic microenvironment points to sustained activation of nucleotide receptors (P2 receptors) capable of generating a persistent pain message. P2X3 receptor, expressed in sensory neurons, mediates nociceptive, neuropathic, and inflammatory pain, and is enrolled in endometriosis-related pain. Pharmacological inhibition of P2X3 receptor is under evaluation as a pain relief treatment for women with endometriosis. The role of other ATP receptors is also discussed here, e.g., P2X4 and P2X7 receptors, which are involved in inflammatory cell–nerve and microglia–nerve crosstalk, and therefore in inflammatory and neuropathic pain. Adenosine receptors (P1 receptors), by contrast, mainly play antinociceptive and anti-inflammatory roles. Purinome-targeted drugs, including nucleotide receptors and metabolizing enzymes, are potential non-hormonal therapeutic tools for the pharmacological management of endometriosis-related pain.

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Central adenosine A₁ receptors inhibit cough via suppression of excitatory glutamatergic and tachykininergic neurotransmission

Cited by 4 publications

References 87 publications

Limonene-induced activation of A2A adenosine receptors reduces airway inflammation and reactivity in a mouse model of asthma

Limonene-induced activation of A2A adenosine receptors reduces airway inflammation and reactivity in a mouse model of asthma

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

Purinergic Signaling in Endometriosis-Associated Pain

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Central adenosine A1 receptors inhibit cough via suppression of excitatory glutamatergic and tachykininergic neurotransmission

Cited by 4 publications

References 87 publications

Limonene-induced activation of A2A adenosine receptors reduces airway inflammation and reactivity in a mouse model of asthma

Limonene-induced activation of A2A adenosine receptors reduces airway inflammation and reactivity in a mouse model of asthma

A Cold Environment Aggravates Cough Hyperreactivity in Guinea Pigs With Cough by Activating the TRPA1 Signaling Pathway in Skin

Purinergic Signaling in Endometriosis-Associated Pain

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Central adenosine A₁ receptors inhibit cough via suppression of excitatory glutamatergic and tachykininergic neurotransmission