Regulation of pharmacology by hetero-oligomerization between A1 adenosine receptor and P2Y2 receptor

Suzuki, Tateo; Namba, Kazunori; Tsuga, Hirofumi; Nakata, Hajime

doi:10.1016/j.bbrc.2006.10.075

Cited by 64 publications

(46 citation statements)

References 16 publications

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“…A study similar to that described in section III.B.2 was done for the pair of adenosine A 1 and P2Y 2 receptors (Suzuki et al, 2006). Coimmunoprecipitation experiments of detergent-solubilized receptors provided evidence that these receptors directly associate in cotransfected HEK293T cells.…”

Section: B Adenosine Receptor Heteromersmentioning

confidence: 98%

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

Fredholm¹,

IJzerman²,

Jacobson³

et al. 2011

Pharmacol Rev

1,926

2,797

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Section: B Adenosine Receptor Heteromersmentioning

confidence: 98%

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

Fredholm¹,

IJzerman²,

Jacobson³

et al. 2011

Pharmacol Rev

1,926

2,797

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“…However, an additional 22 to 26% of large diameter A␤ fibers responded to UTP, suggesting that P2Y 2 receptors also may be directly involved in the transmission of low-threshold mechanical inputs to the spinal cord. It is also possible that activation of a recently described hetero-oligomeric P2Y 2 /ADO A 1 receptor complex (Suzuki et al, 2006) may also negatively modulate the antinociceptive effects of ADO A 1 receptor agonists (McGaraughty and Jarvis, 2006).…”

Section: P2y Receptorsmentioning

confidence: 99%

Painful Purinergic Receptors

Donnelly‐Roberts¹,

McGaraughty²,

Shieh³

et al. 2007

J Pharmacol Exp Ther

155

109

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Multiple P2 receptor-mediated mechanisms exist by which ATP can alter nociceptive sensitivity following tissue injury. Evidence from a variety of experimental strategies, including genetic disruption studies and the development of selective antagonists, has indicated that the activation of P2X receptor subtypes, including P2X 3 , P2X 2/3 , P2X 4 and P2X 7 , and P2Y (e.g., P2Y 2 ) receptors, can modulate pain. For example, administration of a selective P2X 3 antagonist, A-317491, has been shown to effectively block both hyperalgesia and allodynia in different animal models of pathological pain. Intrathecally delivered antisense oligonucleotides targeting P2X 4 receptors decrease tactile allodynia following nerve injury. Selective antagonists for the P2X 7 receptor also reduce sensitization in animal models of inflammatory and neuropathic pain, providing evidence that purinergic glial-neural interactions are important modulators of noxious sensory neurotransmission. Furthermore, activation of P2Y 2 receptors leads to sensitization of polymodal transient receptor potential-1 receptors. Thus, ATP acting at multiple purinergic receptors, either directly on neurons (e.g., P2X 3 , P2X 2/3 , and P2Y receptors) or indirectly through neural-glial cell interactions (P2X 4 and P2X 7 receptors), alters nociceptive sensitivity. The development of selective antagonists for some of these P2 receptors has greatly aided investigations into the nociceptive role of ATP. This perspective highlights some of the recent advances to identify selective P2 receptor ligands, which has enhanced the investigation of ATP-related modulation of pain sensitivity.Pain is a multidimensional sensory process that, acutely, is physiologically adaptive in response to dangerous (e.g., sharp, hot, or chemical stimuli) stimuli in the environment. Persistent pain can range from increased sensitivity to mildly painful stimuli (hyperalgesia) or to otherwise innocuous stimuli (allodynia) (Honore and Jarvis, 2006). It is well appreciated that distinct sensory mechanisms contribute to physiological pain, to pain arising from tissue damage (inflammatory or nociceptive pain), and to pain arising from injury to the nervous system (neuropathic pain). Nociceptive pain is caused by the ongoing activation of A-␦ and C-nociceptors in response to a noxious stimulus. It can be further classified into visceral pain, superficial somatic pain, and deep somatic pain (Honore and Jarvis, 2006;Perl, 2007).Tissue injury results in the release of pronociceptive mediators that sensitize peripheral nerve terminals that can ultimately lead to increased excitability of spinal cord dorsal horn neurons. As such, injury-induced sensitization of peripheral nerves facilitates a sensitization of the central nervous system. A multitude of receptors, transmitters, second messenger systems, transcription factors, and other signaling molecules are now appreciated to be involved in pain pathways (Honore and Jarvis, 2006;Perl, 2007).The ability of ATP (Fig. 1) to modulate neural functio...

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“…Data are means ± SEM for six replicate determinations (n = 3-5): *p < 0.05, **p < 0.01 Several studies have shown that A 1 receptors and A 2A receptors can form homomers [46,47] or A 1 -A 2A heteromers [48]. A 1 -P2Y 1 and A 1 -P2Y 2 adenosine-receptor-ATP-receptor G-protein heteromers have also been reported [49,50]. This receptor dimerisation may lead to alterations in downstream signalling and cellular responses to P1 receptor agonists, potentially contributing to the different effects observed between cell types.…”

Section: Discussionmentioning

confidence: 98%

Lack of effect of adenosine on the function of rodent osteoblasts and osteoclasts in vitro

Hajjawi

Patel

Corcelli

et al. 2016

Purinergic Signalling

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Extracellular ATP, signalling through P2 receptors, exerts well-documented effects on bone cells, inhibiting mineral deposition by osteoblasts and stimulating the formation and resorptive activity of osteoclasts. The aims of this study were to determine the potential osteotropic effects of adenosine, the hydrolysis product of ATP, on primary bone cells in vitro. We determined the effect of exogenous adenosine on (1) the growth, alkaline phosphatase (TNAP) activity and bone-forming ability of osteoblasts derived from the calvariae of neonatal rats and mice and the marrow of juvenile rats and (2) the formation and resorptive activity of osteoclasts from juvenile mouse marrow. Reverse transcription polymerase chain reaction (RT-PCR) analysis showed marked differences in the expression of P1 receptors in osteoblasts from different sources. Whilst mRNA for the A 1 and A 2B receptors was expressed by all primary osteoblasts, A 2A receptor expression was limited to rat bone marrow and mouse calvarial osteoblasts and the A 3 receptor to rat bone marrow osteoblasts. We found that adenosine had no detectable effects on cell growth, TNAP activity or bone formation by rodent osteoblasts in vitro. The analogue 2-chloroadenosine, which is hydrolysed more slowly than adenosine, had no effects on rat or mouse calvarial osteoblasts but increased TNAP activity and bone formation by rat bone marrow osteoblasts by 30-50 % at a concentration of 1 μM. Osteoclasts were found to express the A 2A , A 2B and A 3 receptors; however, neither adenosine (≤100 μM) nor 2-chloroadenosine (≤10 μM) had any effect on the formation or resorptive activity of mouse osteoclasts in vitro. These results suggest that adenosine, unlike ATP, is not a major signalling molecule in the bone.

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Regulation of pharmacology by hetero-oligomerization between A1 adenosine receptor and P2Y2 receptor

Cited by 64 publications

References 16 publications

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

Painful Purinergic Receptors

Lack of effect of adenosine on the function of rodent osteoblasts and osteoclasts in vitro

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