Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.14.16.2 (tyrosine hydroxylase)
14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tyrosine hydroxylase activity in noradrenergic neurons of the locus coeruleus was found to rise in bilaterally adrenalectomized adult mice, with maximum increase of the enzyme activity (52% above control) occurring 7 days after the surgery. No such increase of tyrosine hydroxylase activity was found in dopaminergic neurons of the substantia nigra. The increase of enzyme activity in the locus coeruleus following adrenalectomy was totally prevented by corticosterone replacement. Moreover, the adrenalectomy effect was abolished by hypophysectomy, indicating the involvement of the pituitary rather than the adrenocortical function. Chronic administration of ACTH (20 IU/kg, i.p., daily) resulted in an increase of tyrosine hydroxylase activity in the locus coeruleus, with a time course and magnitude similar to those found after adrenalectomy. Additionally, the effects of four ACTH analogs were determined. ACTH 1-24 and ACTH 4-10 were as effective as the whole ACTH molecule, whereas ACTH 4-10,7-D-Phe and ACTH 11-24 were ineffective. The effect of ACTH 4-10, a peptide fragment with no adrenocorticotrophic activity, further indicates that glucocorticoids are not involved. From these data, it appears that tyrosine hydroxylase in the locus coeruleus neurons is under the regulatory influence of pituitary ACTH. It remains to be determined whether the hormone can be transported from its pituitary origin to the locus coeruleus and exerts a direct action on the noradrenergic neurons. Regardless of the mechanism, the response of the noradrenergic neurons to pituitary activity may be an important component in physiological adaptation of the central nervous system to chronic stress.
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PMID:Influence of ACTH on tyrosine hydroxylase activity in the locus coeruleus of mouse brain. 614 10

Synthesis of catecholamines was measured in slices of frontal cortex, hypothalamus, striatum, hippocampus and brainstem by the accumulation of [3H]norepinephrine (NE) and [3H]dopamine (DA) following incubation with [3H]tyrosine. Following acute footshock (60 shocks, 0.3 mA 30 min), consistent increases in [3H]DA accumulation were seen in frontal cortex slices, but no significant effect was seen in striatal slices. The accumulation of [3H]NE was not altered consistently in frontal cortex, hypothalamus, hippocampus or brainstem. Brain slices from mice adrenalectomized 24-48 h before footshock showed similar results. However, in hypophysectomized mice, footshock did not increase the [3H]DA accumulation in slices of frontal cortex. Administration of dexamethasone before footshock prevented the footshock-induced increase in frontal cortex [3H]DA accumulation, but footshock then significantly increased [3H]NE accumulation in the hypothalamus and brainstem. Chronic footshock (5 days) had little effect on frontal cortex [3H]catecholamine accumulation but produced a consistent elevation of [3H]NE accumulation in slices from the hypothalamus. In confirmation that the slice data reflected in vivo metabolism, both dihydroxyphenylacetic acid and homovanillic acid were significantly elevated in the frontal cortex but not the striatum of mice receiving acute footshock. Since previous studies have shown that ACTH administered intracerebroventricularly also accelerated [3H]DA accumulation in frontal cortex slices, these results are consistent with the involvement of ACTH in the effects of footshock on frontal cortex DA. The effects of chronic footshock are consistent with the activation of hypothalamic tyrosine hydroxylase by corticosterone.
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PMID:Footshock treatment activates catecholamine synthesis in slices of mouse brain regions. 669 46

Subacute exposure of male rats to various concentrations (70-1000 ppm) of dichloromethane (DCM) produces a selective reduction of dopamine (DA) levels without a change of DA turnover in certain types of forebrain DA nerve terminal systems. In the low concentration (70 ppm) a selective reduction of DA turnover was observed in the medial palisade zone (MPZ) of the median eminence. This chlorinated organic solvent also produced a discrete dose-dependent increase of noradrenaline (NA) turnover within the anterior periventricular hypothalamic area and with the highest concentration an increase of NA turnover in the anteromedial frontal cortex. DCM reduced NA levels dose-dependently in the posterior periventricular hypothalamic area and also reduced NA levels in the dorsomedial hypothalamic nucleus (1000 ppm). Following tyrosine hydroxylase inhibition DCM produced an inversely dose-related increase of serum LH levels and at the highest concentration an increase of ACTH secretion was observed. It is suggested that DCM can produce discrete changes in amine storage and turnover in catecholamine (CA) nerve terminal systems of the tel- and diencephalon, some of which may contribute to the DCM induced disturbances of the secretion of anterior pituitary hormones but actions on other transmitter-identified neurons involved in neuroendocrine regulation must also be considered.
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PMID:Central catecholamine neurons and exposure to dichloromethane. Selective changes in amine levels and turnover in tel- and diencephalic DA and NA nerve terminal systems and in the secretion of anterior pituitary hormones in the male rat. 670

The aim of these studies was to determine the intraadrenal mechanism of interleukin-1 (IL-1)-induced corticosterone release from the rat adrenal gland. To accomplish this, the role of catecholamines and eicosanoids on IL-1-induced corticosterone release was determined. Experiments were conducted on primary cultures of dispersed rat adrenal cells. Dose-dependent increases (P < 0.05) in corticosterone concentration were observed when primary adrenal cells were incubated with different doses (10(-10) to 10(-8) M) of IL-1 alpha. IL-1 alpha and IL-1 beta elevated corticosterone release after a 24 hr incubation period. ACTH elevated corticosterone levels at 4 and 24 hr. The stimulatory effect of IL-1 on corticosterone release was mimicked by epinephrine (1 microM), and was selectively blocked by the alpha-adrenergic antagonist, phentolamine (10 microM). The beta-adrenergic antagonist, propranolol (10 microM), did not change IL-1 induced corticosterone release. Neither phentolamine nor propranolol had an effect on ACTH stimulated corticosterone release. Both IL-1 alpha and IL-1 beta significantly elevated (P < 0.05) epinephrine levels after a 24 hr incubation period compared to media-treated controls. Untreated adrenal cells fixed for immunohistochemical staining with a specific anti-rat tyrosine hydroxylase antibody indicate that the primary adrenal cell preparation contained 3.1 +/- 0.45% tyrosine hydroxylase positive cells. On the ultrastructural level, the chromaffin cells were found to be in direct cellular contact with cortical cells. Although IL-1 alpha significantly increased (P < 0.05) prostaglandin E2 (PGE2) levels from primary adrenal cells, the presence of the cyclooxygenase inhibitor, indomethacin (10 microM) significantly inhibited IL-1 alpha-induced PGE2 secretion without altering the effect of IL-1 alpha on corticosterone release. Inhibitors of the lipoxygenase system (5-lipoxygenase, 10 microM) and the lipoxygenase and cytochrome P450 monooxygenase systems (nordihydroguaiaretic acid, 10 microM) did not effect IL-1 alpha-induced corticosterone or PGE2 release. These observations indicate that IL-1 stimulates the local release of catecholamines, which, in turn, stimulates corticosterone release through an alpha-adrenergic receptor; this mechanism is independent of PGE2.
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PMID:Mechanisms of interleukin-1-induced hormone secretion from the rat adrenal gland. 758 87

Basal and stress-induced pituitary-adrenocortical (PA) and sympathetic adrenomedullary (SAM) function was investigated in rats exposed to chronic intermittent cold stress (4 degrees C for 4 h a day for 21 days; CHR). We found that basal plasma levels of corticosterone (B), corticosteroid-binding-globulin, ACTH, epinephrine (E) and norepinephrine (NE) were similar in CHR and control (CTL) animals. In contrast, activity of the adrenal catecholamine-synthesizing enzyme tyrosine hydroxylase, but not phenylethanolamine-N-methyl transferase, was significantly elevated in CHR compared to CTL. Following exposure to a heterotypic stressor (20 min restraint), plasma levels of B were significantly higher in CHR than CTL, but the stress-induced levels of E and NE were not different between groups. These data suggest that, although basal PA function is not altered by exposure to chronic intermittent cold stress, components of the SAM system are affected by this paradigm, and that co-ordinate facilitation of both PA and SAM responses to a novel stressor is not a necessary consequence of exposure to chronic intermittent stress.
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PMID:Effects of chronic intermittent cold stress on pituitary adrenocortical and sympathetic adrenomedullary functioning. 777 96

The results of the present study demonstrate that administration of the ACTH-(4-9) analogue Org 2766 acutely enhances behavioral, morphological, and biochemical recovery after nigrostriatal destruction. Animals treated with Org 2766 (10 micrograms/kg every 24 hr) demonstrated an acceleration of denervation supersensitivity and a significantly decreased ipsilateral rotational response, as compared to their saline counterparts. Upon evaluation of the mesolimbic DA system using open field behavior, peptide-treated rats demonstrated a compensatory response in their rearing behavior. Furthermore, tyrosine hydroxylase immunocytochemical analysis indicated an enhanced staining in the Org 2766-treated groups. This evaluation was confirmed and quantified using specific high-affinity dopamine uptake. The brains of animals treated with Org 2766 maintained higher uptake levels, suggesting a greater fiber density than the saline-treated animals. Although recovery via reinnervation is very unlikely in this short period of time, improved recovery may be the result of a protective effect of Org 2766 after administration of 6-OHDA into the substantia nigra. Thus, it appears that Org 2766 provides the rapid effects in this system, by both accelerating some compensatory mechanisms necessary for functional recovery and promoting cell survival by providing neuronal protection. However, it does not appear that this protection is due to NMDA receptor manipulation. Org 2766 neither mimicked the NMDA antagonist MK-801 behaviorally nor biochemically in binding displacement studies. Interestingly, other studies have suggested that only the full ACTH molecule, and fragments larger than ACTH-(1-17), demonstrated binding activity at micromolar concentrations, whereas the shorter, noncorticotropic fragments were either less active or inactive (Table 2). As for ACTH-(4-10) immunoreactivity, it appears that this neurotrophic fragment of ACTH reappears in adults following injury to the nigrostriatal system. In addition, the systemically administered ACTH-(4-9) analogue, Org 2766, seems to be gaining access to the CNS, but is only effective in the injured system. Therefore, based on the immunocytochemical localization of the ACTH-(4-10) fragment in neonatal brains and in the injured adult rat CNS, the interesting possibility may be raised that endogenous ACTH peptides appear during both ontogeny and regeneration. These studies demonstrate once again that biological responses to the family of ACTH/MSH peptides depend on the specific peptide fragment administered, its dosage, and the timing of the administration. Consequently, since early intervention is of vital importance in CNS recovery processes, synergistic administration of ACTH fragments and other neurotrophic agents may offer a viable approach with which to combat degeneration in the CNS.
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PMID:Specificity versus redundancy of melanocortins in nerve regeneration. 783 97

ACTH peptide fragments demonstrate potent neurotrophic effects on peripheral nerves in situ, central neurons in culture, and have been implicated to have effects on central neurons in vivo. Neurotoxic lesioning of the nigrostriatal system, which depletes the striatum of dopamine, provides a feasible model of central regeneration in which to test these peptides. Male Sprague-Dawley rats were lesioned unilaterally with 6-hydroxydopamine (8 micrograms/4 microliters), infused into the substantia nigra. They were subsequently treated with 10 micrograms/kg IP of Org 2766 [ACTH/MSH(4-9) analogue] or saline every 24 h starting immediately after the infusion and were observed for 2 weeks. Rotational behavior data indicate that Org 2766 significantly decreases ipsiversive turning (p < 0.05), induced by amphetamine (2 mg/kg), as well as accelerating the onset of denervation supersensitivity induced by apomorphine (0.05 mg/kg). Evaluation of dopamine immunohistochemistry, using an anti-tyrosine hydroxylase antibody, demonstrates an enhanced intensity of staining in the ORG 2766-treated tissue compared to its saline counterpart. This difference is confirmed and quantified through specific high-affinity dopamine uptake. Dopamine uptake is about 17% higher in the striata of animals treated with Org 2766. Higher dopamine uptake levels in these ACTH-treated animals correlate with greater fiber density in this group. Therefore, it appears that treatment with the ACTH/MSH(4-9) analogue Org 2766 (10 micrograms/kg/24 h) offers a protective effect from 6-OHDA lesions in the substantia nigra as well as accelerating various compensatory mechanisms involved in functional recovery.
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PMID:Rapid neurotrophic actions of an ACTH/MSH(4-9) analogue after nigrostriatal 6-OHDA lesioning. 790 91

The behavioral and/or neuroendocrine reactivity to psychological (open-field exposure) and physiological (CRF challenge) stimulations, as well as adrenal tyrosine hydroxylase (TH) and phenylethanolamine N-methyl transferase (PNMT) activities were measured, at different ages, in the Roman high avoidance (RHA) and Roman low avoidance (RLA) rat lines that have been genetically selected on the basis of their divergent active avoidance behavior. The highest locomotor activity in the open field, associated to blunted prolactin and renin reactivity to an emotional stress and lower specific TH and PNMT activities, characterized the RHA rats of all ages. HPA axis reactivity to psychological and/or physiological stimulations was identical in young animals (14 weeks old) of the two lines. Nevertheless, it displayed with age maturation processes, since the amplitude of postopen-field secretion peak for ACTH was larger in RLA rats from 20 weeks on, the response to CRF being not increased until 42 weeks. These maturation processes could result from genetically influenced changes related to environmental stimulations. Therefore, the Roman lines may be an excellent model to study the interactions between the genetic and developmental factors controlling the coupling between both behavioral and neuroendocrine functions.
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PMID:Maturation of the behavioral and neuroendocrine differences between the Roman rat lines. 798 61

Peptides that regulate the growth of tissues, whether in a positive or negative manner, are termed growth factors. The melanocortins, neurotrophic sequences that correspond to peptide fragments contained within ACTH-(1-13), beneficially affect neural growth during development and regeneration. Analogues of ACTH-(4-9) (Org 2766) and ACTH-(4-10) (BIM 22015) are capable of sustaining neurite outgrowth from cultured dorsal root ganglion and spinal cord cells in the absence of nerve growth factor. The development of sexually dimorphic behavior in both male and female rats is influenced by perinatal administration of ACTH. This change appears to be correlated with changes in the growth and metabolism of developing serotonergic and dopaminergic systems in the hypothalamic nuclei associated with male and female sexual behavior. Similar melanotropic influences are found in the developing neuromuscular system. Neuromuscular development is accelerated by perinatal administration of melanocortins, provoking both nerve and muscle to attain early maturation. However, the responding tissue varies pivotally with age: early in gestation, embryonic muscle is acutely sensitive to peptide exposure; but once innervation has occurred, only the developing nerve reacts to melanocortin treatment. Melanocortins have little if any effect on the normal, adult neuromuscular system. Following peripheral nerve injury or pathology, melanotropins once again become effective growth factors, accelerating and enhancing nerve regeneration and muscle reinnervation. Electrophysiological, morphological, biochemical, and functional tests all indicate that ACTH-(4-10), Org 2766, BIM 22015, and alpha-MSH improve various facets of nerve regeneration, the degree to which the specific parameter is improved being dependent on the peptide fragment, its dosage, and pattern of administration. BIM 22015, while less effective as a neurotrophic factor, has potent myotrophic effects that the other peptides lack. Org 2766 may provide some protective action to the injured CNS as demonstrated by tests of cognitive function following brain lesions, although evaluation of recovery is sometimes enigmatic. Recovery from destruction of the nigrostriatal system is more easily measured through tests of motor function and open field behavior, both of which support a protective role for Org 2766. Compensatory mechanisms, including the presence of increased tyrosine hydroxylase and greater density of dopaminergic fibers, may be involved. Melanocortins are effective growth factors in sciatic nerve regeneration in neonatal rats. Both alpha-MSH and ACTH-(4-10) favor the formation of morphologically normal end plates despite the trauma following nerve crush at postnatal day 2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Melanotropins as growth factors. 839 Jan 55

Systemically administered nicotine elicits ACTH release indirectly by acting on neurons in brainstem catecholaminergic regions known to send afferent projections to the paraventricular nucleus of the hypothalamus (PVN), the site of CRH neurons involved in initiating ACTH secretion. The present study in rats examined 1) the relationship between dose-dependent expression of cFos in the PVN and that in the nucleus of the solitary tract (NTS)-A2, NTS-C2 and locus coeruleus (LC), after iv nicotine (0.045-0.18 mg/kg, administered at 0.09 mg/kg per min); 2) the dependence of PVN cFos expression on the effects of nicotine in brainstem, using the nicotinic cholinergic antagonist, mecamylamine, administered into the fourth ventricle; and 3) the extent of catecholaminergic involvement in the effect of nicotine on the PVN, measured by immunocytochemical double-labeling for cFos and tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. The results showed that the magnitude of cFos expression was dependent on the dose of nicotine in all regions studied (P < 0.0006); however, at the two lowest doses, only the NTS and CRH-containing region of the PVN expressed cFos, whereas the LC and the rest of the PVN were activated only by higher doses. Nicotine also elicited a dose-dependent increase in cFos expression in the TH+ neurons of the NTS, with C2 more sensitive than A2. Interestingly, the majority of NTS neurons expressing cFos were noncatecholaminergic, implicating other transmitter systems. Fourth ventricular mecamylamine completely blocked nicotine-induced cFos expression throughout the NTS, as well as the PVN. The results provide further support for the idea that catecholaminergic afferents from the NTS, but not the LC, play a significant, albeit not an exclusive, role in the activation of the PVN in response to nicotine.
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PMID:Nicotine-induced cFos expression in the hypothalamic paraventricular nucleus is dependent on brainstem effects: correlations with cFos in catecholaminergic and noncatecholaminergic neurons in the nucleus tractus solitarius. 859 11


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