Mechanical stimulus-evoked signal transduction between keratinocytes and sensory neurons via extracellular ATP

The spatial segregation of the plasma membrane plays a prominent role in distinguishing and sorting a large number of signals a cell receives simultaneously. The plasma membrane comprises regions known as lipid rafts, which serve as signal-transduction hubs and platforms for sorting membrane-associated proteins. Ca2+-binding proteins of the annexin family have been ascribed a role in the regulation of raft dynamics. Glycosylphosphatidylinositol-anchored 5′-nucleotidase is an extracellular, raft-associated enzyme responsible for conversion of extracellular ATP into adenosine. Our results point to a regulation of ecto-5′-nucleotidase activity by Ca2+-dependent, annexin-mediated stabilization of membrane rafts.

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Signal transduction and white cell maturation via extracellular ATP and the P2Y 11 receptor

Immunology and Cell Biology ◽

10.1046/j.1440-1711.2000.00918.x ◽

2000 ◽

Vol 78 (4) ◽

pp. 369-374 ◽

Cited By ~ 20

Author(s):

Louise Van Der Weyden ◽

Arthur D Conigrave ◽

Michael B Morris

Keyword(s):

Signal Transduction ◽

Extracellular Atp ◽

White Cell ◽

Cell Maturation

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Cutaneous Sensory Neurons Expressing the Mrgprd Receptor Sense Extracellular ATP and Are Putative Nociceptors

Journal of Neurophysiology ◽

10.1152/jn.01396.2007 ◽

2008 ◽

Vol 99 (4) ◽

pp. 1581-1589 ◽

Cited By ~ 43

Author(s):

G. Dussor ◽

M. J. Zylka ◽

D. J. Anderson ◽

E. W. McCleskey

Keyword(s):

Sensory Neurons ◽

Sensory Modality ◽

Atp Release ◽

Extracellular Atp ◽

Stratum Granulosum ◽

P2x3 Receptors ◽

Long Duration ◽

Mouse Dorsal Root Ganglion ◽

Mu Opioids ◽

External Stimuli

Sensory neurons expressing the Mrgprd receptor are known to innervate the outermost living layer of the epidermis, the stratum granulosum. The sensory modality that these neurons signal and the stimulus that they respond to are not established, although immunocytochemical data suggest they could be nonpeptidergic nociceptors. Using patch clamp of dissociated mouse dorsal root ganglion (DRG) neurons, the present study demonstrates that Mrgprd+ neurons have several properties typical of nociceptors: long-duration action potentials, TTX-resistant Na+ current, and Ca2+ currents that are inhibited by mu opioids. Remarkably, Mrgprd+ neurons respond almost exclusively to extracellular ATP with currents similar to homomeric P2X3 receptors. They show little or no sensitivity to other putative nociceptive agonists, including capsaicin, cinnamaldehyde, menthol, pH 6.0, or glutamate. These properties, together with selective innervation of the stratum granulosum, indicate that Mrgprd+ neurons are nociceptors in the outer epidermis and may respond indirectly to external stimuli by detecting ATP release in the skin.

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P1 and P2 purinergic receptor signal transduction in rat type II pneumocytes

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.2.901 ◽

1989 ◽

Vol 66 (2) ◽

pp. 901-905 ◽

Cited By ~ 25

Author(s):

D. Warburton ◽

S. Buckley ◽

L. Cosico

Keyword(s):

Signal Transduction ◽

Purinergic Receptor ◽

Rank Order ◽

Extracellular Atp ◽

Type Ii ◽

Camp Production ◽

Receptor Signal ◽

Type Ii Pneumocytes ◽

Alpha Beta ◽

Pi Hydrolysis

Extracellular ATP is a potent agonist of surfactant phosphatidylcholine (PC) exocytosis from type II pneumocytes in culture. We studied P1 and P2 receptor signal transduction in type II pneumocytes. The EC50 for ATP on PC exocytosis was 10(-6) M, whereas the EC50 for ADP, AMP, adenosine, and the nonmetabolizable ATP analogue alpha,beta-methylene ATP was 10(-4) M. The rank order of agonists for PC exocytosis was ATP greater than ADP greater than AMP greater than adenosine greater than alpha,beta-methylene ATP. The rank order of agonists for phosphatidylinositol (PI) hydrolysis was ATP greater than ADP, whereas AMP, adenosine, and alpha,beta-methylene ATP did not stimulate PI hydrolysis. ATP (10(-4) M) caused a 15-fold increase in adenosine 3′,5′-cyclic monophosphate (cAMP) production, and the nonmetabolizable adenosine analogue 5′-N-ethylcarboxyamidoadenosine (10(-6) M) increased cAMP production threefold. The effects of both these agonists on cAMP production were completely inhibited by the adenosine antagonist 8-phenyltheophylline (10(-5) M). The effects of ATP (10(-4) M) on PC exocytosis were inhibited 38% by 10(-5) M 8-phenyltheophylline. Thus, ATP regulates PC exocytosis by activating P2 receptors, which stimulate PI hydrolysis to inositol phosphate, as well as by activating P1 receptors, which stimulate cAMP production. Interactions between the P1 and P2 pathways may explain the high potency of extracellular ATP as an agonist of PC exocytosis.

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Signal Transduction by P2-Purinergic Receptors for Extracellular ATP

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/ajrcmb/4.4.295 ◽

1991 ◽

Vol 4 (4) ◽

pp. 295-300 ◽

Cited By ~ 129

Author(s):

George R. Dubyak

Keyword(s):

Signal Transduction ◽

Purinergic Receptors ◽

Extracellular Atp ◽

P2 Purinergic Receptors

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Benzolamide, acetazolamide, and signal transduction in avian intrapulmonary chemoreceptors

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.279.6.r1988 ◽

2000 ◽

Vol 279 (6) ◽

pp. R1988-R1995 ◽

Cited By ~ 16

Author(s):

S. C. Hempleman ◽

T. A. Rodriguez ◽

Y. A. Bhagat ◽

R. S. Begay

Keyword(s):

Signal Transduction ◽

Carbonic Anhydrase ◽

Action Potential ◽

Single Cell ◽

Sensory Neurons ◽

Anas Platyrhynchos ◽

Discharge Rate ◽

Normal Function ◽

Extracellular Recordings ◽

Intrapulmonary Chemoreceptors

Intrapulmonary chemoreceptors (IPC) are CO2-sensitive sensory neurons that innervate the lungs of birds, help control the rate and depth of breathing, and require carbonic anhydrase (CA) for normal function. We tested whether the CA enzyme is located intracellularly or extracellularly in IPC by comparing the effect of a CA inhibitor that is membrane permeable (iv acetazolamide) with one that is relatively membrane impermeable (iv benzolamide). Single cell extracellular recordings were made from vagal filaments in 16 anesthetized, unidirectionally ventilated mallards ( Anas platyrhynchos). Without CA inhibition, action potential discharge rate was inversely proportional to inspired Pco 2 (−9.0 ± 0.8 s−1 · lnTorr−1; means ± SE, n = 16) and exhibited phasic responses to rapid Pco 2 changes. Benzolamide (25 mg/kg iv) raised the discharge rate but did not alter tonic IPC Pco 2 response (−9.8 ± 1.6 s−1 · lnTorr−1, n = 8), and it modestly attenuated phasic responses. Acetazolamide (10 mg/kg iv) raised IPC discharge, significantly reduced tonic IPC Pco 2 response to −3.5 ± 3.6 s−1 · lnTorr−1 ( n = 6), and severely attenuated phasic responses. Results were consistent with an intracellular site for CA that is less accessible to benzolamide. A model of IPC CO2 transduction is proposed.

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Extracellular ATP stimulates three different receptor-signal transduction systems in FRTL-5 thyroid cells. Activation of phospholipase C, and inhibition and activation of adenylate cyclase

Biochemical Journal ◽

10.1042/bj2830281 ◽

1992 ◽

Vol 283 (1) ◽

pp. 281-287 ◽

Cited By ~ 46

Author(s):

K Sato ◽

F Okajima ◽

Y Kondo

Keyword(s):

Signal Transduction ◽

Cyclic Amp ◽

Adenylate Cyclase ◽

Phospholipase C ◽

Pertussis Toxin ◽

Extracellular Atp ◽

Thyroid Cells ◽

Receptor Signal ◽

Atp Analogues ◽

Signal Transduction Systems

In FRTL-5 thyroid cells, extracellular ATP, a P2-agonist, not only stimulates phospholipase C but also inhibits forskolin- or thyrotropin (TSH)-induced stimulation of adenylate cyclase in a pertussis toxin-sensitive manner [Okajima, Sato, Nazarea, Sho, & Kondo (1989) J. Biol. Chem. 264, 13029-13037]. We have now found that, in pertussis toxin-treated cells, ATP can directly stimulate adenylate cyclase. Although adenylate cyclase modulation occurs through ATP metabolites such as AMP and adenosine, we show that extracellular ATP itself also regulates cyclic AMP production, based on the following: (1) the actions of ATP were imitated by hydrolysis-resistant ATP analogues, (2) the elimination of adenosine by adenosine deaminase decreased the effect of ATP only partially, at least at concentrations greater than 10 microM-ATP, and (3) the amount of AMP produced from ATP was too low to account for the ATP effects. To identify the respective receptors for the three different actions of ATP, we established an antagonist profile. Suramin, which has been reported to be a P2-receptor antagonist, inhibited ATP-induced phospholipase C activation in a competitive fashion, but did not affect ATP-induced adenylate cyclase modulation. On the other hand, 8-cyclopentyl-1,3-diphenylxanthine competitively antagonized both the stimulatory and inhibitory ATP actions on cyclic AMP levels, but did not influence the activation of phospholipase C by ATP. The order of potency for various xanthine derivatives was clearly different with respect to their antagonistic effects on the stimulation and inhibition of adenylate cyclase induced by ATP. We conclude that ATP activates three receptors, each of which is coupled to a different signal transduction system in FRTL-5 cells, i.e. phospholipase C activation, and adenylate cyclase activation and inhibition.

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