EFFECTS OF EXTRANEURONAL ACCUMULATION OF ISOPRENALINE ON CAMP PRODUCTION IN PERFUSED RAT-HEART

The effects of extraneuronal accumulation of isoprenaline on the level of cAMP in perfused rat hearts were investigated. When catechol-O-methyl transferase (COMT) was intact perfusion with isoprenaline (10–6 M) for 5 min and 30 min (low accumulation of isoprenaline in the heart) enhanced the cAMP level. Propranolol (10–6 M) significantly decreased the high level of cAMP produced by the perfusion with isoprenaline for 5 min and 30 min (low accumulation of isoprenaline). When COMT was inhibited by tropolone, perfusion with isoprenaline (10–6 M) for 5 min (slight accumulation of isoprenaline in the heart) slightly increased the level of cAMP, while perfusion for 30 min (high accumulation of isoprenaline in the heart) did not increase the level of cAMP. Propranolol (10–6 M) significantly decreased the cAMP level produced by 5 min perfusion with isoprenaline, but did not change the level by 30 min perfusion. The perfusion length (5 min and 30 min) and COMT inhibition by tropolone (10–4 M) in the absence of isoprenaline did not affect cAMP levels. These results suggest that extraneuronally accumulated isoprenaline may inhibit the adenylate cyclase in perfused rat hearts. © 1990, The Japanese Pharmacological Society. All rights reserved.