title: The temporal relationship between glycogen phosphorylase and activation of the pyruvate dehydrogenase complex during adrenaline infusion in resting canine skeletal muscle.
abstract: The present study examined the effect of adrenaline infusion on the activation status of glycogen phosphorylase and the pyruvate dehydrogenase complex (PDC) and on the accumulation of glucose-6-phosphate (G-6-P) and acetylcarnitine in resting canine skeletal muscle. The study was performed in an effort to gain some insight into the temporal relationship between glycogen phosphorylase and PDC activation in vivo in skeletal muscle, which is currently unresolved. Multiple muscle samples were obtained from canine brachial muscle (n = 10) before and during (1, 3, 7 and 15 min) adrenaline infusion (0.14 microg (kg body mass)(-1) min(-1), I.V.). Adrenaline infusion increased glycogen phosphorylase "a" by > 2-fold above basal levels after 3 min (pre-infusion = 9.2 +/- 1.1 vs. 3 min = 22.3 +/- 4.0 mmol glucosyl units (kg dry muscle)(-1) min(-1), P < 0.05). The concentration of G-6-P increased transiently from its basal concentration at 1 min (pre-infusion = 1.5 +/- 0.2 vs. 1 min = 4.4 +/- 0.9 mmol kg dry muscle)(-1), P < 0.01), declined to its pre-infusion concentration at 3 min (P < 0.05), and then increased again after 7 min of infusion (P < 0.05). The PDC was activated following 7 min of adrenaline infusion (pre-infusion = 0.22 +/- 0.04 vs. 7 min = 1.04 +/- 0.15 mmol acetyl-CoA (kg wet muscle)(-1) min(-1), P < 0.01), and this degree of activation was maintained for the duration of infusion. During the first 3 min of infusion, the concentration of acetylcarnitine declined (pre-infusion = 3.8 +/- 0.3 vs. 3 min = 1.6 +/- 0.2 mmol (kg dry muscle)(-1), P < 0.05), before transiently increasing at 7 min above the 3 min concentration (3 min = 1.6 +/- 0.2 vs. 7 min = 5.1 +/- 1.0 mmol (kg dry muscle)(-1), P < 0.01). This is the first study to demonstrate that adrenaline can indirectly activate the PDC in skeletal muscle in vivo at rest. The results demonstrate that adrenaline increased glycogen phosphorylase activation and glycolytic flux within 3 min of infusion, but took several more minutes to activate the PDC. This temporal relationship, combined with a probable adrenaline-induced increase in metabolic rate (and thereby resting ATP demand), resulted in the biphasic changes in G-6-P and acetylcarnitine with infusion time.
authors.affiliation: School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. p.roberts@nottingham.ac.uk
authors.forename: Paul A
authors.initials: PA
authors.lastname: Roberts
authors.forename: Susan J G
authors.initials: SJ
authors.lastname: Loxham
authors.forename: Simon M
authors.initials: SM
authors.lastname: Poucher
authors.forename: Dumitru
authors.initials: D
authors.lastname: Constantin-Teodosiu
authors.forename: Paul L
authors.initials: PL
authors.lastname: Greenhaff
mesh_terms: D000108:Acetylcarnitine / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology*; D005260:Female; D019298:Glucose-6-Phosphate / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D012146:Rest; D013997:Time Factors
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D019298:Glucose-6-Phosphate; D000108:Acetylcarnitine; D024981:Glycogen Phosphorylase; D004837:Epinephrine