Release synthesis, enzyme-induced

The mechanism of action of 13-cis retinoic acid in normal and diseased human skin has not been studied. Many biological effects of vitamin A, especially its ability to labilize biological membranes and release lysosomal enzymes, have been described in detail. Vitamin A and its derivatives control cell growth and differentiation in epithelial tissues. Retinoic acid, in particular, is a potent stimulator of mitosis in the epidermis. Excess vitamin A and its derivatives also have been demonstrated to inhibit keratinization and induce a mucous metaplasia with enhanced glycoprotein synthesis in several laboratory models, such as embryonic chick skin in organ culture . The mode of action of topical retinoic acid in acne is thought to be the increased production of nonadherent surface scales, which prevents follicular occlusion and comedo formation . None of the known effects, however, can fully explain the apparent disease and individual specificity of the clinical response to 13-cis retinoic acid nor do they explain its ability to reduce the erythema in these diseases. 

CCK is found in the digestive tract and the central and peripheral nervous systems. In the brain, CCK coexists with DA. In the peripheral nervous system, the two principal physiological actions of CCK are stimulation of gaU. bladder contraction and pancreatic enzyme secretion. CCK also stimulates glucose and amino acid transport, protein and DNA synthesis, and pancreatic hormone secretion. In the CNS, CCK induces hypothermia, analgesia, hyperglycemia, stimulation of pituitary hormone release, and a decrease in exploratory behavior. The CCK family of neuropeptides has been impHcated in anxiety and panic disorders, psychoses, satiety, and gastric acid and pancreatic enzyme secretions. 

The apparent reliance of enzyme activation on phosphorylation and intracellular Ca + gives a clue as to how the rate of 5-HT synthesis might be coupled to its impulse-evoked release. Certainly, the impulse-induced increase in intracellular Ca +, and/or activation of the G protein-coupled receptors that govern synthesis of cAMP, could modify the activity of tryptophan hydroxylase. Indeed, this could explain why activation of either somal 5-HTia autoreceptors in the Raphe nuclei (which depress the firing rate of 5-HT neurons) or terminal 5-HTib autoreceptors (which depress 5-HT release) can reduce the production of cAMP and attenuate 5-HT synthesis. 

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

The effect of Li+ upon the synthesis and release of acetylcholine in the brain is equivocal Li+ is reported to both inhibit and stimulate the synthesis of acetylcholine (reviewed by Wood et al. [162]). Li+ appears to have no effect on acetyl cholinesterase, the enzyme which catalyzes the hydrolysis of acetylcholine [163]. It has also been observed that the number of acetylcholine receptors in skeletal muscle is decreased by Li+ [164]. In the erythrocytes of patients on Li+, the concentration of choline is at least 10-fold higher than normal and the transport of choline is reduced [165] the effect of Li+ on choline transport in other cells is not known. A Li+-induced inhibition of either choline transport and/or the synthesis of acetylcholine could be responsible for the observed accumulation of choline in erythrocytes. This choline is probably derived from membrane phosphatidylcholine which is reportedly decreased in patients on Li+ [166],... 

The concentration of Li+ in the thyroid is three to four times that in serum [179]. It is thought that Li+ may be concentrated in the thyroid gland by a mechanism similar to the incorporation of iodide, I-, resulting in competition between Li+ and I the levels of intracellular 1 decrease when those of Li+ increase, and vice versa [182]. Li+ inhibits both the ability of the gland to accumulate 1 and the release of iodine from the gland. In vitro, Li+ has no effect on thyroid peroxidase, the enzyme that catalyzes the incorporation of I" into tyrosyl residues leading to thyroidal hormone synthesis, but does increase the activity of iodotyrosine-deio-dinase, which catalyzes the reductive deiodination of iodotyrosyls, thus maintaining the levels of intracellular I [182]. The increase in iodoty-rosine-deiodinase activity is probably a response to the Li+-induced decrease in the concentration of thyroidal I". Li+ has no effect on the conversion of thyroxine to triiodothyronine. The overall effect of this competition between Li+ and 1 is, therefore, reduced levels of thyroid hormone in the presence of Li+. 

Chapter 22) are released from the adrenal glands. By inducing enzyme synthesis, these hormones increase the amounts of a variety of enzymes within the cells of target organs such as the liver. Glucocorticoids also appear to increase the sensitivity of cell responses to cAMP and hence to hormones such as glucagon.268... 

The major route of degradation of tyrosine in animals begins with transamination (Fig. 25-5, reaction c) to p-hydroxyphenylpyruvate. The enzyme tyrosine aminotransferase94 is induced in the liver in response to the action of glucorticoid hormones (Chapter 22). The synthesis of the enzyme is also controlled at the translational level, release of the newly formed protein from liver ribosomes being stimulated by cyclic AMP. The enzyme is subject to posttranscriptional... 

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