Basal and drug-induced cAMP levels in cortical slices from the tottering mouse

Basal and drug-induced levels of cAMP were determined in cortical slices from mice which were homozygous for the tottering (tg/tg) gene defect as well as from co-isogenic controls (+/+). Basal levels of cAMP were 77 +/- 16% higher in tg/tg slices compared to the controls. This difference was abolished by exposure of the slices to propranolol, a beta-adrenergic receptor antagonist. Both isoproterenol and veratridine stimulated cAMP formation, but only small differences were observed in the cAMP levels in tg/tg and +/+ slices after this treatment. Of the veratridine-dependent increase in cAMP, approximately 40% was blocked by propranolol treatment of slices from both strains. The results suggest that a higher level of endogenous norepinephrine release in tottering mice contributes to an elevation of basal cAMP levels.