Effects of high KCI, isoproterenol, NaF and forskolin on noradrenaline release from cerebral cortical slices of adult and senescent rats.

Perfusion of isoproterenol (100 ?M), 10mM NaF or 100 ?M forskolin significantly enhanced release of l-[(3)H]noradrenaline (NA) compared to the spontaneous release from cerebral cortical slices of adult rats. Isoproterenol-induced release was reduced by propranolol (100 ?M). In the Ca(2) + free medium and in the Ca(2+) free medium containing 2.0 mM EGTA, the release enhanced by isoproterenol, NaF or forskolin was not different from that in the normal medium. In contrast, the marked reduction in 30 mM KCI-evoked release was observed in both Ca(2+) -deficient media. It is suggested that ?-adrenoceptor-stimulatory GTP-binding protein-adenylate cyclase system locating at presynaptic sites positively modulates NA release presumably by the mechanism other than increasing Ca(2+) influxes. Furthermore, the cerebral cortical l-[(3)H]NA uptake and the release induced by isoproterenol, NaF and forskolin as well as KCI and metamphetamine were significantly reduced at senescent stage compared to those at the adult stage, suggesting that presynaptic functions regarding the release as well as the uptake, could reduce with age.