Release of noradrenaline from rabbit atria by isoprenaline and histamine

The release of noradrenaline accompanying positive inotropic and chronotropic actions of isoprenaline and histamine was investigated in rabbit atria in which the transmitter stores were labelled with (2H)-noradrenaline. Propranolol (3 microM) significantly reduced the isoprenaline (1 microM)-induced release of radioactivity and positive inotropic and chronotropic actions. Cimetidine (30 microM) significantly reduced the histamine (25 microM)-induced release of radioactivity and positive inotropic and chronotropic actions. Tetrotoxin (0.9 microM) significantly reduced the release of radioactivity by both isoprenaline and histamine but did not affect the positive inotropic and chronotropic actions of these drugs. The results suggest that conducted action potentials are associated with isoprenaline- and histamine-induced release of noradrenaline and it is possible that the sympathetic nerves are ephaptically stimulated by increased myocardial activity.