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)