title: Greater glycogen utilization during 1- than 2-adrenergic receptor stimulation in the isolated perfused rat heart.
abstract: Differences in energy metabolism during beta(1)- and beta(2)-adrenergic receptor (AR) stimulation have been shown to translate to differences in the elicited functional responses. It has been suggested that differential access to glycogen during beta(1)- compared with beta(2)-AR stimulation may influence the peak functional response and modulation of the response during sustained adrenergic stimulation. Interleaved (13)C- and (31)P-NMR spectroscopy was used during beta(1)- and beta(2)-AR stimulation at matched peak workload (2.5 times baseline) in the isolated perfused rat heart to monitor glycogen levels, phosphorylation potential, and intracellular pH. Simultaneous measurements of left ventricular (LV) function [LV developed pressure (LVDP)], heart rate (HR), and rate-pressure product (RPP = LVDP x HR) were also performed. The heart was perfused under both substrate-free (SF) conditions and with exogenous glucose (G). The greater glycogenolysis was observed during beta(1)- than beta(2)-AR stimulation with G (54% vs. 38% reduction, P = 0.006) and SF (92% vs. 79% reduction, P = 0.04) perfusions. The greater beta(1)-AR-mediated glycogenolysis was correlated with greater ability to sustain the initial contractile response. However, with SF perfusion, the duration of this ability was limited: excessive early glycogen depletion caused an earlier decline in LVDP and phosphorylation potential during beta(1)- than beta(2)-AR stimulation. Therefore, endogenous glycogen stores are depleted earlier and to a greater extent, despite a slightly weaker overall inotropic response, during beta(1)- than beta(2)-AR stimulation. These findings are consistent with beta(1)-AR-specific PKA-dependent glycogen phosphorylase kinase signaling.
authors.affiliation: Laboratory of Clinical Investigation, Box 29, Gerontology Research Center 4D-08, 5600 Nathan Shock Dr., Baltimore, MD 21 224, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: McConville
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: Richard G
authors.initials: RG
authors.lastname: Spencer
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017298:Bisoprolol / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D050261:Glycogenolysis / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D010725:Phosphocreatine; C002904:zinterol; D006003:Glycogen; D005947:Glucose; D009638:Norepinephrine; D011224:Prazosin; D017298:Bisoprolol