Independent sensitization of beta-adrenoceptors and adenylate cyclase in acute myocardial ischaemia.
1. Acute myocardial ischaemia provokes sensitization of the adenylate cyclase system. This sensitization could be differentiated in a receptor-linked and an enzyme-linked sensitization. The increase in the number of beta-adrenoceptors in the plasma membranes was observed already after 15 min of global ischaemia (50 +/- 2 to 67 +/- 6 fmol mg-1 protein) and persisted after 50 min of ischaemia. The maximally isoprenaline-stimulated adenylate cyclase activity rose from 66 +/- 7 to 100 +/- 10 pmol cAMP min-1 mg-1 protein after 15 min of global ischaemia indicating the receptor-mediated sensitization of the beta-adrenergic system. However, after 50 min of ischaemia the isoprenaline-stimulated adenylate cyclase was reduced by about 50% despite the continuous increase of beta-adrenoceptors in the plasma membranes. 2. Additionally direct stimulation of the adenylate cyclase by forskolin revealed an increased enzyme activity after 15 min of global ischaemia (300 +/- 20 vs 378 +/- 25 pmol cAMP min-1 mg-1). Prolonged periods of ischaemia, however, caused a decline of the total adenylate cyclase activity (232 +/- 24 pmol cAMP min-1 mg-1 protein). This demonstrates an enzyme-specific sensitization of the adenylate cyclase, which in contrast to the rise in beta-adrenoceptors is only transient. This enzyme-specific sensitization or the late inactivation of the enzyme occur independently of receptor activation and cannot be prevented by beta-adrenoceptor blockade (10(-6) M alprenolol) prior to the ischaemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)
Strasser
R H
RH
Department of Cardiology, University of Heidelberg, FRG.
Marquetant
R
R
Kübler
W
W
D000208:Acute Disease; D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003327:Coronary Disease / Q000201:enzymology / Q000378:metabolism*; D004734:Energy Metabolism; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000227:Adenine Nucleotides; D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D000255:Adenosine Triphosphate; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol