Influence of stimulation parameters on the release of adenosine, lactate and CO2 from contracting dog gracilis muscle.

Abstract

SUMMARY1. The addition of adenosine, CO2 and lactate to the venous blood draining an isolated constant-flow perfused gracilis muscle was studied in anaesthetized and artificially ventilated dogs during twitch and tetanic contractions.2. Venous adenosine concentration increased from 154+33 nm (mean+S.E.M.) to 279 + 121 or 280 + 125 nm after 10 min of 1P5 or 3 Hz twitch contractions and to 240+ 120 or 276+ 139 nm after 10 min of 1 or 5 s tetani occurring at 0 1 Hz. Twitch contractions at 0-1 or 0 5 Hz for 10 min did not significantly elevate venous adenosine.3. Venous lactate concentration was significantly increased after 10 min of 1-5 or 3 Hz twitches or 5 s tetani at 0-1 Hz. There was a good correlation (r = 0 70; P < 0-001) between venous adenosine and lactate concentrations.4. Venous partial pressure of C02 (PC02) was significantly elevated after 10 min of 1P5 or 3 Hz twitch contractions or 1 or 5 s tetani at 0-1 Hz. There was also a good correlation (r = 0-58; P < 0-001) between venous adenosine concentration and Pco2.5. Venous partial pressure of 02 (PO2) decreased during all contractions except those at 0-1 Hz, but the oxygen cost per unit of tension x time was similar during every pattern of stimulation, and the percentage of the total energy production achieved by anaerobic means during muscle contractions did not exceed that at rest, indicating that there had been no limitation to the oxygen supply. Venous Po2 was poorly correlated with venous adenosine concentration (r = 028), but quite well correlated with venous lactate concentration (r = 0-53; P < 0 001). If the indirect influence of Po2 on venous adenosine concentration via an increase in lactate concentration was eliminated by partial correlation, then the coefficient for the relationship between venous adenosine concentration and venous Po2 became 0-15.6. There was a significant correlation between the venous adenosine concentration and the venous pH (r = 0 53; P < 0-001). If the influence of oxygenation on venous adenosine and pH was eliminated by partial correlation, the coefficient for the relationship between venous adenosine and pH increased to 0-95.

Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle.

“…A similar effect of adenosine receptor antagonism by either 8-cyclopentyl-1,3-dipropylxanthine (CPDPX)' or 8-phenyltheophylline was observed on 2-deoxy-[3H]glucose transport or phosphorylation (20). On the other hand, it is well known that muscle adenosine production and release are markedly enhanced during contractions, particularly in slow oxidative muscle fibers (21,22), probably leading to adenosine receptor-mediated vasodilation oflocal vascular beds (21 ). Furthermore, adenosine has been demonstrated to enhance insulin-stimulated glucose uptake and transport in adipocytes (23)(24)(25) and in myocardium (26,27).…”

“…Such a shift is likely to be accelerated by contractions, via a further activation of muscle glucose transport rate on the one hand, and via activation of glycogenolysis on the other hand. (b) Slow oxidative muscle fibers are characterized by the highest rates ofadenosine production and release (21,22,38), which, in view of the present findings, is likely to glucose uptake measured before and after 5 min of electrical stimulation in hindlimbs perfused with no insulin added to the perfusion mix at a constant flow of 15 Caffeine was used as a tool for the study ofadenosine receptor function in regulating glucose uptake and transport in resting and contracting skeletal muscle. Caffeine is one of the oldest and still most used "drugs" in society.…”

“…This observation, however, does not exclude adenosine receptors to regulate insulin-mediated glucose uptake in muscle at rest. The low rates ofadenosine release from well-oxygenated muscles in the resting state, in contrast to muscle during electrical stimulation (21,22,38), may be insufficient to cause significant adenosine receptor activation in a resting hindlimb preparation. Therefore, we studied the effect of A1 receptor agonism on glucose uptake in hindquarters perfused with insulin in the perfusion mix.…”

The Role of Intracellular pH in the Control of Adenosine Output from Red Skeletal Muscle

“…Another study employed a wide range of different twitch and tetanic contraction fre quencies in order to vary the adenosine out put from the muscle: adenosine was again lin early correlated with pH, but not with any of the recognised indices of muscle oxygenation, such as venous PCH or oxygen supply-todemand ratio [13]. Several authors have noted that the relationship between adenosine and oxygen is curved: adenosine output re mains constant as PCH decreases, until the oxygen reaches some critical value, then aden osine output increases exponentially [3,13] ( fig. 3).…”

Purinergic signalling-evoked intracellular Ca2+ concentration changes in the regulation of chondrogenesis and skeletal muscle formation

“…The major source of adenosine formation in skeletal muscle is AMP 5'-nucleotidase, which dephosphorylates AMP. In the muscle interstitium, adenosine has been reported to appear as the result of nucleotide degradation within the skeletal muscle fibres and released to the extracellular space in response to contractions [45]. Adenosine receptor transcripts have been identified in skeletal muscle homogenates decades ago; a high expression level of A 2A receptor mRNA, moderate signals for A 2B , and no signals for A 1 and A 3 receptors have been reported [46].…”