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

---

Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymatic activity of tyrosine hydroxylase (EC 1.14.16.2) increases in rat pheochromocytoma PC18 cells exposed to either elevated levels of cyclic AMP or glucocorticoids. The cyclic AMP-mediated increase in activity is elicited by cyclic AMP analogs or by compounds which activate adenylate cyclase or inhibit phosphodiesterase. The glucocorticoid-mediated increase is elicited only by glucocorticoid steroid hormones; nonglucocorticoid steroid hormones have no effect on tyrosine hydroxylase. In PC18 cells exposed simultaneously to both cyclic AMP-elevating agents and glucocorticoids, the increase in tyrosine hydroxylase activity is greater than that observed in cells treated with optimal concentrations of either inducing agent alone. Immunochemical titration experiments demonstrate that the increases in tyrosine hydroxylase activity observed in cells treated with the cyclic AMP analog, 8-bromocyclic AMP, and/or the synthetic glucocorticoid, dexamethasone, are due to increases in enzyme protein. Time course studies show that in cells treated with either 8-bromocyclic AMP or dexamethasone, the enzyme level increases slowly to a level 5-7-fold greater than that observed in untreated cells after 4 days of treatment. In cells treated with both of these inducing agents simultaneously, the enzyme level increases to a level 10-12-fold greater than that observed in control cells after 4 days of treatment. This additive increase in activity in cells treated with both inducing agents is observed at all time points. The rates of synthesis and degradation of tyrosine hydroxylase have also been measured in PC18 cells, using an antiserum to tyrosine hydroxylase to rapidly isolate radiolabeled enzyme from cells that have been incubated in the presence of [3H]leucine. The apparent half-life of tyrosine hydroxylase in the PC18 cells is approximately 30 hr. In PC18 cells incubated in the presence of radiolabeled leucine for 60 min, 0.2-0.3% of the total soluble protein synthesized is identified as tyrosine hydroxylase. In cells treated with either 8-bromocyclic AMP or dexamethasone for 24 hr, there is a 6-8-fold increase in the rate of synthesis of the enzyme. In cells treated with both inducing agents simultaneously, there is a 10-12-fold increase in the rate of synthesis; thus, the additive increase in enzyme level observed in cells treated with both inducing agents is paralleled by an additive increase in the rate of synthesis of the enzyme in these cells.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Induction of tyrosine hydroxylase by cyclic AMP and glucocorticoids in a rat pheochromocytoma cell line: effect of the inducing agents alone or in combination on the enzyme levels and rate of synthesis of tyrosine hydroxylase. 243 Jan 69

The hypothesis that dopamine (DA) autoreceptors modulate the phosphorylation of tyrosine hydroxylase (TH; EC 1.14.16.2) was investigated in rat striatal slices. Tissue was prelabeled with 32P inorganic phosphate, and TH recovered by immunoprecipitation with anti-TH rabbit serum. The TH monomer was resolved on sodium dodecyl sulfate polyacrylamide gels, and the extent of phosphorylation was determined by scanning densitometry of autoradiographs. Depolarization of striatal slices with 55 mM K+ markedly increased the incorporation of 32P into several proteins, including the TH monomer (Mr = 60,000). A similar increase in TH phosphorylation occurred in response to the adenylate cyclase activator forskolin and the cyclic AMP analog dibutyryl cyclic AMP. An increase in TH phosphorylation was not observed in response to the D1-selective agonist SKF 38393. The D2-selective DA autoreceptor agonist pergolide decreased the phosphorylation of TH below basal levels and blocked the increase in phosphorylation elicited by 55 mM K+. The inhibitory effect of pergolide was antagonized by the D2-selective antagonist eticlopride. Changes observed in the phosphorylation of TH were mirrored by changes in tyrosine hydroxylation in situ. These observations support the hypothesis that a reduction in TH phosphorylation is the mechanism by which DA autoreceptors modulate tyrosine hydroxylation in nigrostriatal nerve terminals.
...
PMID:Dopamine autoreceptors modulate the phosphorylation of tyrosine hydroxylase in rat striatal slices. 256 75

This study examined the consequences of alcohol (ethanol) exposure during fetal life on lesion-induced dopaminergic synapse responsiveness (plasticity) in the olfactory tubercle of the adult rat. Normally, in the olfactory tubercle, olfactory bulbectomy elicits alterations in pre- and postsynaptic dopaminergic markers, including, respectively, (1) increased tyrosine hydroxylase activity and immunoreactivity, which is associated with dopaminergic axon sprouting, and (2) increased dopaminergic receptor density and potentiated dopamine activation of adenylate cyclase. We have utilized biochemical and quantitative immunocytochemical methodology to examine these synaptic markers in olfactory bulbectomized or sham-operated adult rats. These animals were offspring of dams which were administered one of the following diets during pregnancy: (1) liquid diet containing 35% ethanol-derived calories ad libitum; (2) liquid diet containing an isocaloric amount of maltose-dextrin instead of ethanol, pair-fed; or (3) unaltered liquid diet ad libitum. The results show that prenatal alcohol exposure leads to suppression of the lesion-elicited dopaminergic synapse responsiveness in the olfactory tubercle. There were no significant differences between offspring born to control and pair-fed animals, indicating that the observed abnormalities were not due to alterations in their nutritional status. In conclusion, the present data are a biochemical and quantitative immunocytochemical demonstration of impaired lesion-induced synaptic responsiveness. This renders a new dimension in support of previous evidence indicating that prenatal alcohol exposure leads to altered neuroanatomical, neuroendocrinological and behavioral responsiveness to various challenges. Such impaired synaptic responsiveness may underlie brain functional abnormalities characteristic of fetal alcohol syndrome.
...
PMID:Prenatal ethanol exposure impairs lesion-induced plasticity in a dopaminergic synapse after maturity. 256 76

In homogenates of rat nucleus accumbens, quinpirole, a dopamine (DA) D2 receptor agonist, inhibited the activation of tyrosine hydroxylase (TH) elicited by either forskolin, an activator of adenylate cyclase, or rolipram, a cyclic nucleotide phosphodiesterase inhibitor. The inhibition produced by 1 microM quinpirole was completely antagonized by the D2 blocker L-sulpiride (2 microM). Quinpirole failed to inhibit the stimulation of TH elicited by dibutyryl cyclic AMP (2 mM), which acts independently of adenylate cyclase. Quinpirole (10 microM) significantly inhibited the stimulation of adenylate cyclase activity elicited by 1 microM forskolin. These results indicate that mesolimbic DA autoreceptors can regulate TH activity by inhibiting a presynaptic adenylate cyclase system.
...
PMID:Involvement of adenylate cyclase inhibition in dopamine autoreceptor regulation of tyrosine hydroxylase in rat nucleus accumbens. 257 Nov 11

We compared the response of rat PC12 cells and a derivative PC18 cell line to the effects of adenosine receptor agonists, antagonists, and adenine nucleotide metabolizing enzymes. We found that theophylline (an adenosine receptor antagonist), adenosine deaminase, and AMP deaminase all decreased basal cyclic AMP content and tyrosine hydroxylase activity in the PC12 cells, but not in PC18 cells. Both cell lines responded to the addition of 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine, adenosine receptor agonists, by exhibiting an increase in tyrosine hydroxylase activity and cyclic AMP content. The latter finding indicates that both cell lines contained an adenosine receptor linked to adenylate cyclase. We found that the addition of dipyridamole, an inhibitor of adenosine uptake, produced an elevation of cyclic AMP and tyrosine hydroxylase activity in both cell lines. Deoxycoformycin, an inhibitor of adenosine deaminase, failed to alter the levels of cyclic AMP or tyrosine hydroxylase activity. This suggests that uptake was the primary inactivating mechanism of adenosine action in these cells. We conclude that both cell types generated adenine nucleotides which activate the adenosine receptor in an autocrine or paracrine fashion. We found that PC12 cells released ATP in a calcium-dependent process in response to activation of the nicotinic receptor. We also measured the rates of degradation of exogenous ATP, ADP, and AMP by PC12 cells. We found that the rates of metabolism of the former two were at least an order of magnitude greater than that of AMP. Any released ATP would be rapidly metabolized to AMP and then more slowly degraded to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Adenosine receptor activation and the regulation of tyrosine hydroxylase activity in PC12 and PC18 cells. 257 81

Evidence is presented indicating that a cAMP-dependent mechanism activates tryptophan hydroxylase (TrpH), the rate-limiting enzyme for serotonin (5-HT) biosynthesis. Forskolin, a selective activator of adenylate cyclase, stimulated 5-HT formation in synaptoneurosome preparations of rat striatum, substantia nigra, hypothalamus, and amygdala. Further studies of striatum revealed that the forskolin-induced activation of serotonin synthesis is readily reversible. Also, it may be self-limited by a mechanism of desensitization, since after an initial exposure to forskolin followed by removal, a re-exposure of synaptoneurosomes to forskolin was no longer stimulatory. In contrast to these results for 5-HT synthesis, forskolin-induced stimulation of dopamine synthesis persisted following removal of forskolin; hence the response was not rapidly reversible or desensitized. In soluble extracts of striatum, 8-thiomethyl-cyclic AMP enhanced TrpH activity, supporting a direct role of cyclic AMP and cyclic AMP-dependent protein kinase in regulating TrpH. In agreement with previous reports, 8-thiomethyl cyclic AMP also stimulated tyrosine hydroxylase activity in soluble striatal extracts. We conclude that cyclic AMP is an important regulator of TrpH, in addition to its known effects on tyrosine hydroxylase.
...
PMID:Regulation of tryptophan hydroxylase activity by a cyclic AMP-dependent mechanism in rat striatum. 282 48

The effects of streptozotocin-induced diabetes on the retinal dopaminergic system have been examined in Long-Evans (pigmented) rats. Tyrosine hydroxylase activity was significantly decreased while dopamine-stimulated adenylate cyclase was increased in 2-month-diabetic rats. The observed increase in dopamine-stimulated adenylate cyclase activity in diabetic retinae may be related to neurotransmitter receptor changes because postreceptor activation of adenylate cyclase by guanylyl imidodiphosphate was not altered.
...
PMID:Dopamine-stimulated adenylate cyclase and tyrosine hydroxylase in diabetic rat retina. 286 Sep 52

Release of adrenal catecholamine by carbachol has been shown to be coincident with an increase in intracellular cAMP levels. Bovine adrenal medullary (BAM) cells were prepared and maintained in culture and used to examine the role of cAMP in stimulus-secretion coupling. The addition of ACTH to these cells caused a 10- to 50-fold increase in cellular cAMP without an effect on catecholamine secretion, suggesting cortical cell contamination. Percoll density separation of both BAM cells and adrenal cortical cells revealed that the greatest cAMP responses to ACTH corresponded to the catecholamine-containing cell fractions and not to those density layers where cortical cells sedimented. BAM cells isolated on Percoll did not metabolize [14C]cholesterol to steroids as would be expected were the ACTH-stimulated cAMP accumulations due to cortical cell contamination of the cultures. ACTH stimulated protein phosphorylation in 32P-labeled BAM cells in a manner indistinguishable from that induced by carbachol and forskolin. The major soluble phosphoprotein to be affected by these agents had a relative mol wt of 55-57 kdaltons on sodium dodecyl sulfate-gels and corresponded to tyrosine hydroxylase, which is a specific marker enzyme in the adrenal for chromaffin cells. We propose that bovine adrenal chromaffin cells express ACTH receptors which are coupled to adenylate cyclase. While no acute effect of ACTH was found on catecholamine secretion, ACTH may play a direct role in the regulation of catecholamine synthesis by stimulating the phosphorylation of tyrosine hydroxylase by cAMP-dependent protein kinase.
...
PMID:Direct effects of adrenocorticotropic hormone on bovine adrenomedullary cells: adenosine 3',5'-monophosphate-dependent phosphorylation of tyrosine hydroxylase. 286 12

The effect of BHT 920, a putative presynaptic dopamine receptor agonist, on tyrosine hydroxylase was investigated in rats. The activity of the high affinity (BH4) form of striatal tyrosine hydroxylase was investigated dose-dependent manner in rats treated with BHT 920. This effect was pronounced in the dopaminergic system and was not observed to the same extent in the adrenal medulla. In vitro, BHT 920 had no effect upon striatal tyrosine hydroxylase activity. BHT 920 also did not affect either striatal adenylate cyclase activity or the extent of its stimulation by dopamine. The results concerning tyrosine hydroxylase were complemented by measurements of dopamine and DOPA in the striatal and the limbic system. The reduction in DOPA accumulation and in the high affinity form of tyrosine hydroxylase activity elicited by BHT 920 could be blocked by haloperidol, suggesting that BHT 920 may interact with the D2 dopamine receptor although a functional antagonism could not be ruled out. The present results suggest that BHT 920 may exert a specific effect upon tyrosine hydroxylase in dopaminergic nervous tissue which is not mediated by alpha 2-adrenoceptors.
...
PMID:Evidence for a specific effect of BHT 920, an azepine derivative, on tyrosine hydroxylase in the dopaminergic system of the rat. 287 43

The modulation of 3,4-dihydroxyphenylethylamine (dopamine, DA) synthesis and release in rabbit retina in vitro by high K+; adenylate cyclase activators such as forskolin, 2-chloroadenosine, vasoactive intestinal polypeptide (VIP); and the putative DA autoreceptor agonist N-n-propyl-3-(3-hydroxyphenyl) piperidine (3-PPP) has been investigated. Incubation of retinas in 50 mM K+ resulted in the activation of tyrosine hydroxylase (TH). Activation did not require the presence of extracellular Ca2+. K+ 50 mM also induced a Ca2+-dependent release of DA. Forskolin 50 microM stimulated TH but 100 microM 2-chloroadenosine and 650 nM VIP did not. Individually, (+)-3-PPP, (-)-3-PPP, and (+/-)-3-PPP reduced DA synthesis and increased its release. The effects of (+/-)-3-PPP were dose-dependent and did not require the presence of extracellular Ca2+. The activation of TH induced by 50 mM K+, but not that induced by 50 microM forskolin, was abolished by 100 microM (+/-)-3-PPP.
...
PMID:Investigation of dopamine content, synthesis, and release in the rabbit retina in vitro: II. Effects of high potassium, adenylate cyclase activators, and N-n-propyl-3-(3-hydroxyphenyl) piperidine. 287 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---