An estimate of adenosine triphosphate release into the venous effluent from exercising human forearm muscle

Forrester, T

doi:10.1113/jphysiol.1972.sp009915

Cited by 141 publications

(83 citation statements)

References 21 publications

(20 reference statements)

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“…Extracellular ATP rises to >10 µM when a muscle contracts without blood flow (27). We find that a transient appearance of such extracellular ATP can greatly increase ASIC3 current even for minutes after the ATP is removed (Figure 7).…”

Section: Paradox Number 2 Answered: Coincident Detection Of Lactate mentioning

confidence: 87%

An acid-sensing ion channel that detects ischemic pain

Naves

McCleskey

2005

Braz J Med Biol Res

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Ischemic pain occurs when there is insufficient blood flow for the metabolic needs of an organ. The pain of a heart attack is the prototypical example. Multiple compounds released from ischemic muscle likely contribute to this pain by acting on sensory neurons that innervate muscle. One such compound is lactic acid. Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid. In rats, it is expressed only in sensory neurons and then only on a minority (~40%) of these. Nevertheless, it is expressed at extremely high levels on virtually all dorsal root ganglion sensory neurons that innervate the heart. It is extraordinarily sensitive to protons (Hill slope 4, half-activating pH 6.7), allowing it to readily respond to the small changes in extracellular pH (from 7.4 to 7.0) that occur during muscle ischemia. Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons. This final property makes ASIC3 a "coincidence detector" of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia.

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Section: Paradox Number 2 Answered: Coincident Detection Of Lactate mentioning

confidence: 87%

An acid-sensing ion channel that detects ischemic pain

Naves

McCleskey

2005

Braz J Med Biol Res

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“…2011). During exercise in normal environmental conditions, plasma ATP also increases in the forearm and leg circulations (Forrester & Lind, 1969; Forrester, 1972; González‐Alonso et al . 2002; Mortensen et al .…”

Section: Introductionmentioning

confidence: 99%

Blood temperature and perfusion to exercising and non‐exercising human limbs

González‐Alonso

Calbet

Boushel

et al. 2015

Experimental Physiology

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New Findings What is the central question of this study? Temperature‐sensitive mechanisms are thought to contribute to blood‐flow regulation, but the relationship between exercising and non‐exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non‐exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature‐ and metabolism‐sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature‐sensitive mechanisms may contribute to blood‐flow regulation, but the influence of temperature on perfusion to exercising and non‐exercising human limbs is not established. Blood temperature (T B), blood flow and oxygen uptake (trueV˙O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher T B and limb trueV˙O2. Leg and arm vascular conductance during exercise compared with rest was related closely to T B (r 2 = 0.91; P < 0.05), plasma ATP (r 2 = 0.94; P < 0.05) and limb V˙normalO2 (r 2 = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in T B and limb trueV˙O2, whereas ABF, arm T B and V˙normalO2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in trueV˙O2. In 12 trained males, increases in femoral T B and LBF during incremental leg exercise were mirrored by similar pulmonary artery T B and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data reveal a close coupling among perfusion, T B and aerobic metabolism in exercising and non‐exercising extremities and a tight association between limb vasodilatation and increases in plasma ATP. These findings suggest that temperature and V˙normalO2 contribute to the regulation of limb perfusion through control of intravascular ATP.

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“…However, ATP may also be released from stimulated postsynaptic cells. This has been observed in crayfish (Smith & Lindgren, 1986); frog (Abood et al, 1962) and human muscle (Forrester, 1972) as well as in Torpedo electric organ (Israel , 1976). The effects of extracellular ATP on ACh release at mature synapses have been examined in the past.…”

Section: Discussionmentioning

confidence: 99%

Potentiation by endogenously released ATP of spontaneous transmitter secretion at developing neuromuscular synapses in Xenopus cell cultures

Huang

1994

British J Pharmacology

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1 Previously we have shown that extracellular application of ATP, a substance co-stored and coreleased with acetylcholine (ACh) in the peripheral nervous system, markedly potentiated the frequency of spontaneous synaptic currents (SSCs) produced by ACh. In the present study, we have further characterized the purinoceptor which mediates the potentiation effect of ATP and the role of endogenously released ATP.2 Pretreatment with a P2-purinoceptor antagonist, suramin (0.3 mM), but not a PI-purinoceptor antagonist, 8-phenyltheophylline (0.1 mM), prevented the potentiating effect of ATP. 3 We studied the role of endogenously released ATP by examining the effect of a specific P2-purinoceptor antagonist on the frequency of spontaneous synaptic events at high-activity synapses (> 3 Hz) and found that suramin, but not 8-phenyltheophylline markedly reduced the frequency of SSCs at these high-activity synapses. In addition, desensitizing the P2-purinoceptor with x,4-methylene ATP also produced similar effects to suramin. 4 Extracellular application of the L-type Ca2+ channel blockers, verapamil, nifedipine or diltiazem (10 pLM each) reduced SSC frequency of high-activity synapses, while the N-type Ca2+ channel blocker, omega-conotoxin had no appreciable effect. The potentiating effect of ATP was further prevented by pretreatment with the L-type Ca2+ channel blockers. On the other hand, Bay K 8644, which is a depolarization-dependent L-type Ca2+ channel agonist, potentiated SSC frequency at these high-activity synapses.5 These results suggest that endogenous release of ATP at developing neuromuscular synapses is responsible for the maintenance of high levels of spontaneous ACh release, which is known to play a crucial role in regulating postsynaptic differentiation.

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An estimate of adenosine triphosphate release into the venous effluent from exercising human forearm muscle

Cited by 141 publications

References 21 publications

An acid-sensing ion channel that detects ischemic pain

An acid-sensing ion channel that detects ischemic pain

Blood temperature and perfusion to exercising and non‐exercising human limbs

Potentiation by endogenously released ATP of spontaneous transmitter secretion at developing neuromuscular synapses in Xenopus cell cultures

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