Protein kinase activation as an early event in the trans-synaptic induction of tyrosine 3-monooxygenase in adrenal medulla.

Abstract

An increase of cAMP/cGMP concentration ratio is the earliest stimulus-coupled biochemical change that has been measured in the adrenal medulla during the trans-synaptic induction of tyrosine 3-monooxygenase [EC 1.14.16.2; L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating)]. In adrenal medulla of rats receiving reserpine alone (16 Amol/kg intraperitoneally) or reserpine and propranolol (40 Amol/kg intraperitoneally 30 min before reserpine), or exposed to 40 for 4 hr, the extent and duration of the increase of the cAMP/cGMP concentration ratio exceeds the critical value that is required to activate the protein kinases (EC 2.7.1.37; ATP:protein phosphotransferase). Gel filtration experiments indicate that during this activation, the catalytic subunit of the protein kinase (low-molecular-weight enzyme) is released from the holoenzyme. The activation of protein kinase lasts longer than the increase in the cAMP/cGMP concentration ratio and appears to be an obligatory early event that mediates the increase of tyrosine monooxygenase synthesis. The trans-synaptic induction of the monooxygenase in adrenal medulla appears to be due to an increased synthesis of the enzyme; the rate for monooxygenase degradation is proportional to the number of enzyme molecules that are present at various stages of the induction process.

The effect of nerve growth factor on cycle AMP levels in superior cerival ganglia of the rat.

“…It may be possible to correlate the rise in cAMP with the effects on tyrosine hydroxylase. It must be pointed out, however, that the general question of the involvement of cyclic nucleotides in the induction of tyrosine hydroxylase in other systems is controversial (18,19).…”

Activation and nuclear translocation of protein kinase during transsynaptic induction of tyrosine 3-monooxygenase.

“…The protein kinase activity of the pellet is increased between 3 and 17 hr after reserpine injection. Our evidence indicates that this increase is due to a translocation from cytosol to subcellular structures of a kinase that utilizes lysine-rich histone as phosphate acceptor.…”

“…The first event in this induction is an increase in the 3':5'-cyclic AMP (cAMP) content, presumably by the activation of adenylate cyclase (4,7,8). When the synthesis rate of cAMP is enhanced, the number of cytosol protein kinase (EC 2.7.1.37; ATP:protein phosphotransferase) molecules that are activated is also increased (3). In the present paper, we report that in the adrenal medulla the transsynaptic regulation of the expression of the metabolic code is critically dependent on the translocation from cytosol into the nucleus of a low-molecular-weight catalytic subunit of protein kinase.…”

“…The latter not only regulate the polarity of the neuronal membranes, but they also influence the expression of the metabolic code in postsynaptic cells (1). In the rat adrenal medulla, the biosynthesis of tyrosine-3-monooxygenase [EC 1.14.16.2; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] is regulated transsynaptically (2)(3)(4). In chromaffin cells that are presistently (1 hr or more) stimulated by the acetylcholine released by nerve impulses from presynaptic terminals, the monooxygenase is induced 18-24 hr later (2-7).…”

“…In the rat adrenal medulla, the biosynthesis of tyrosine-3-monooxygenase [EC 1.14.16.2; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] is regulated transsynaptically (2)(3)(4). In chromaffin cells that are presistently (1 hr or more) stimulated by the acetylcholine released by nerve impulses from presynaptic terminals, the monooxygenase is induced [18][19][20][21][22][23][24] hr later (2)(3)(4)(5)(6)(7). We have adopted this transsynaptic induction of tyrosine monooxygenase as a model to study the molecular mechanisms whereby the release of acetylcholine regulates the expression of the metabolic code in postsynaptic cells.…”