INDEPENDENT SENSITIZATION OF BETA-ADRENOCEPTORS AND ADENYLATE-CYCLASE IN ACUTE MYOCARDIAL-ISCHEMIA

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) 1990 The British Pharmacological Society