title: Ischemic preconditioning is associated with a delay in ischemia-induced reduction of beta-adrenergic signal transduction in rabbit hearts.
abstract: BACKGROUND
  It has been reported that the A1-adenosine receptor mediates the cardioprotective effect of ischemic preconditioning. This receptor couples inhibitory guanine nucleotide-binding protein (Gi) and inhibits adenylate cyclase activity. However, the role of adenylate cyclase in preconditioning is unknown.
  
  
  RESULTS
  We compared the effects of ischemia on the sarcolemmal beta-adrenergic receptor density (Bmax), the stimulatory guanine nucleotide-binding protein (Gs) activity as determined by reconstitution with S49 lymphoma cyc- membranes, and baseline and maximally stimulated adenylate cyclase activities (ACAs) in control and preconditioned rabbit hearts. The control population (n = 28) received 0, 10, 20, and 60 minutes of coronary occlusion (n = 6 to 8 per stage), and preconditioned rabbits (n = 24) received two cycles of alternating 5-minute occlusion and reperfusion before sustained ischemia (n = 6 per stage). In control hearts, occlusion induced rapid and progressive reductions in the Bmax, Gs, and ACAs after 10 to 60 minutes of ischemia. Preconditioning did not affect the reduction in Bmax, but it preserved reductions in Gs activity and ACAs after 10 to 20 but not 60 minutes of sustained ischemia. In another study, 18 rabbits were treated with pertussis toxin 48 hours before surgery to block Gi. During treatment, no significant difference was observed in the ischemia-induced reduction in ACAs in the ischemic region between control (n = 8) and preconditioned (n = 10) animals after 20 minutes of ischemia.
  
  
  CONCLUSIONS
  Preconditioning delays ischemia-induced reductions in beta-adrenergic signal transduction. Inhibition of ACA is not the target effect of the A1-adenosine receptor-Gi pathway responsible for the cardioprotective role of preconditioning.
authors.affiliation: Department of Internal Medicine, Kyoto University Hospital, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwase
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: S
authors.initials: S
authors.lastname: Miki
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: S
authors.initials: S
authors.lastname: Sasayama
mesh_terms: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D037342:Pertussis Toxin; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012969:Sodium Fluoride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D011943:Receptors, Adrenergic, beta; D018047:Receptors, Purinergic P1; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D012969:Sodium Fluoride; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol