Inhibitory effect of membrane active compounds on induction of tyrosine aminotransferase in chick embryo liver cells in culture.

In the course of investigations on the effect of beta-adrenergic receptor blocking agents in experimental porphyria we observed an inhibitory action of DL-propranolol and other membrane active compounds on the induced activity of delta-aminolevulinate synthetase Q-ALAS) (EC 3.2.1.37) both in vivo and in vitro [l-3] . Beta-adrenergic receptor blocking agents compete with catecholamines for activation of beta-adrenergic receptors. Some of these agents also possess non-specific membrane effects such as changes in depolarisation and/or repolarisation of the cellular membrane, local anesthetic and anti-arhythmic properties, etc. Other drugs, which have no betareceptor blocking effects, including quinidine and lydocain, have non-specific membrane activity and are regarded as membrane active compounds. The various membrane effects of these drugs and of betareceptor blockers are, at least partially, dissimilar. In order to determine whethertheinhibitory effect of DL-propanolol and other membrane active compounds is specific for induction of &-ALAS, we examined their effect on induction of another inducible enzyme, tyrosine aminotransferase (TAT) (EC 2.6.1 S). TAT is a soluble enzyme, the activity of which is increased by administration of steroid hormones with glucocorticoid activity, both in rat liver [4] and in hepatoma cells in culture [5,6]. Dexamethasone is known to be a potent inducer in cultured hepatoma cells. It raises TAT activity 4-8 fold in this system [7,8]. Our experiments were carried out in cultures of chick embryo liver cells.