Electrical pacing induces adenylyl cyclase in skeletal muscle independent of the beta-adrenergic receptor.
Continuous electrical pacing (EP) at 10 Hz of the peroneal nerve innervating fast-twitch muscles of the hindlimb in adult rabbits increases skeletal muscle concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) by 3.1-fold at 10 days and increases beta-adrenergic receptor (beta-AR) density by 2.0-fold at 21 days. To determine whether beta-AR, the alpha-subunit of guanine nucleotide proteins (Gs alpha), or adenylyl cyclase is primarily responsible for pacing-induced increases in muscle cAMP, we measured adenylyl cyclase activity (ACA) in muscles that were electrically paced for 3 (n = 4), 10 (n = 8), and 21 (n = 8) days. EP resulted in a time-dependent increase in ACA that was 2.2 +/- 0.3-fold (P less than 0.005) at 21 days. EP significantly increased GTP-, 5'-guanylylimidodiphosphate-, isoproterenol-, NaF-, and forskolin-stimulated ACA, and propranolol administration to rabbits during EP did not alter pacing-induced changes in ACA. There were no changes in protein concentration, Na(+)-K(+)-adenosinetriphosphatase activity, or Gs alpha with EP. Based on these studies, we conclude that EP appears to increase cAMP through mechanisms independent of the beta-AR and through mechanisms that may involve alterations at the level of adenylyl cyclase.
Kraus
W E
WE
Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710.
Longabaugh
J P
JP
Liggett
S B
SB
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D019204:GTP-Binding Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009132:Muscles / Q000201:enzymology*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D008565:Membrane Proteins; D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase