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

Injection of tranylcypromine and L-tryptophan results in rats displaying behavioural changes including hyperactivity, probably due to stimulation of post-synaptic 5-hydroxytryptamine (5-HT) receptors. Increased locomotor activity of a different type is elicited by injection of tranylcypromine and L-dopa, a procedure which increased dopaminergic function in the brain. It has now been demonstrated that the neuroleptic drugs, chlorpromazine, alpha-flupenthixol, haloperidol and spiroperidol block both syndromes. The inhibition produced by these drugs on 5-HT-induced hyperactivity is probably because a dopaminergic system is involved in the behavioural expression of the 5-HT induced hyperactivity. The structurally related drugs with no neuroleptic activity (ethopropazine, promethazine and beta-flupenthixol)are without effect on thses hyperactivity syndromes. Also ineffective were the neuroleptics pimozide and clozapine. Striatal dopamine sensitive adenylate cyclase activity in vitro was inhibited by the administration of chlorpromazine (100 mg/kg) in vivo. Rats treated for 4 or more days with chlorpromazine, alpha-flupenthixol, spiroperidol and haloperidol subsequently showed enhanced locomotor activity in response to tranylcypromine and L-Dopa. Administration of those drugs which did not block hyperactivity acutely did not result in enhancement. Only chlorpromazine, when given for 4 days, enhanced the hyperactivity response following tranylcypromine and L-tryptophan, probably because the drug also blocks 5-HT receptors. In rats displaying enhanced behavioural responses no evidence was found for enhanced sensitivity of striatal adenylate cyclase to dopamine.
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PMID:Single and repeated administration of neuroleptic drugs to rats: effects on striatal dopamine-sensitive adenylate cyclase and locomotor activity produced by tranylcypromine and L-tryptophan or L-Dopa. 1 27

The effects of L-Dopa and the dopamine receptor stimulant ET-495 on cisternal cAMP levels were studied in rats. L-dopa (100-200 mg/kg) increased cisternal cAMP levels by 60 to 80% of controls. When peripheral Dopa-decarboxylase was inhibited, smaller doses of L-Dopa were effective. Fla-63, an inhibitor of dopamine-beta-hydroxylase lowered the increase induced by L-Dopa which was completely suppressed by propranolol, not by phentolamine, suggesting that the cAMP increase is mediated through a central beta-adrenoceptor stimulation. ET-495 failed to influence cAMP levels which argues against a dopamine-sensitive adenylate cyclase involved in the L-Dopa effect. Moreover, large increases of cisternal cAMP were observed after treatment with theophylline , not papaverine which suggests different effects of these "phosphodiesterase inhibitors" on the cyclic AMP systems in the central nervous system or on transport mechanisms.
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PMID:Cyclic adenosinemonophosphate in cerebrospinal fluid. Effects of theophylline, L-dopa and a dopamine receptor stimulant in rats. 17 61

The adenylate cyclase responses of the human GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors to TRH, LH-RH, biogenic amines, peptides hormones, PGE1 and rat median eminence extract (MEE) have been examined. Out of 4 GH producing pituitary adenomas obtained from patients with active acromegaly at hypophysectomy two were stimulated by TRH, two by LH-RH, three by norepinephrine, one by dopamine, four by PGE1 and none by serotonin. Glucagon stimulated the adenylate cyclase in one of three and MEE in both of two tested. The positive responses of paradoxical GH release after TRH and/or LH-RH before surgery in these patients coincidentally related to the response of adenylate cyclase of each pituitary adenoma. There seems, however, to be no consistent correlation between the adenylate cyclase responses to biogenic amines and the GH release after L-Dopa or 5-hydroxytroptophan tested. The adenylate cyclase of a pituitary adenoma from case of Cushing's disease was stimulated by LH-RH, norepinephrine glucagon and MEE but not by TRH. Plasma levels of ACTH, beta-MSH and cortisol increased after LH-RH but not after TRH in this patient before hypophysectomy. The adenylate cyclase of two ectopic ACTH producing tumors (gastric carcinoid and malignant thymoma) was activated by TRH, LH-RH, norepinephrine, epinephrine, serotonin, PGE1 and MEE. These results indicate the presence of multiple hormone receptors in GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors, and suggest that the paradoxical GH or ACTH release after TRH and/or LH-RH injection in acromegaly and Cushing's syndrome might be caused by an alteration of the cellular membrane receptors of the pituitary adenomas.
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PMID:Adenylate cyclase of GH and ACTH producing tumors of human: activation by non-specific hormones and other bioactive substances. 19 Feb 56

Using tritium-labeled dl(+/-)epinephrine, we have extended previous studies demonstrating binding of epinephrine to human leukocytes. We have now further assessed the biological significance of this catecholamine binding by comparing the specificity of binding by human leukocytes with the ability of these compounds to inhibit epinephrine-stimulated adenyl cyclase. Binding is specific for catechols, but does not distinguish between physiologically active and inactive stereo isomers, nor between alpha- and beta-adrenergic agonists. Although 2.5 X 10(-4) M 1(-)DOPA, dopamine, d(+)epinephrine and serotonin failed to stimulate leukocytic adenyl cyclase and prevented adenyl cyclase stimulation by 2.5 X 10(-4) M 1(-)epinephrine, the inhibition of adenyl cyclase by d(+)epinephrine is noncompetitive. This catechol-binding site is clearly not the beta-adrenergic receptor. Its physiological significance, if any, remains to be elucidated.
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PMID:Specificity studies of leukocytic catecholamine receptors. 20 16

It was shown on albino mice that when DOPA-3H (20 muCi/mouse) was administered before nonradioactive DOPA (1 mg/mouse) tritium accumulation in the tissue of Harding-Passi's melanoma of these mice proved to increase. Melanoma radioactivity in this experimental group was double that in the tumour tissue of the animals to which DOPA-3H alone was administered. Examination of the adenylate cyclase, phosphodiesterase activity and of the level of cAMP in melanoma of mice 2 hours after DOPA administration (1 mg/mouse) showed accumulation of cAMP and an increase in the phosphodiesterase activity; as to adenylate cyclase activity--it fell. It is suggested that DOPA realizes its effect not only as melanin precursor, but also through the cAMP system, influencing the melanogenesis enzymes activity.
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PMID:[Regulatory role of DOPA and components of the cyclic adenosine-3',5'-monophosphate system]. 20 73

The manner in which dyskinesia and intermittency of neurological control had emerged late in the therapy of Parkinsonism with L-3,4-dihydroxyphenylalanine (levodopa) had suggested to us that this drug can imprint on the brain a chemical memory of its passage. The majority of authors ascribed these events to denervation hypersensitivity caused by the nigral and other lesions of the disease. By feeding levodopa to mice, however, we induced a state that simulated denervations hypersensitivity, including hyperreaction to single injections of levodopa and increased dopamine-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in homogenates of caudate nuclei. These phenomena were not caused by actual denervation, because the hypersensitivity declined and disappeared some weeks after the dietary levodopa was stopped.
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PMID:L-3,4-dihydroxyphenylalanine-induced hypersensitivity simulating features of denervation. 26 33

We studied the effect of catecholamines on the adenylate cyclase activity of myogenic cells of the L6 line during the differentiation process. The enzyme of mononucleated myoblasts was found to be activated by adrenaline L, noradrenaline L, and to a small extent, by adrenaline D and dihydrocymandelic acid. The adenylate cyclase of the differentiated cells responded to adrenaline L and noradrenaline L but not to adrenaline D or dihydroxymandelic acid. This activation could be inhibited by the addition of DOPA and propranolol, a specific beta adrenergic blocker. alpha adrenergic compounds such as phentolamine did not have any effect. It is concluded that beta adrenergic receptors are present on myogenic cells before and after differentiation.
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PMID:Hormone responsiveness of adenylate cyclase activity of cultured myogenic cells. 68 75

Proximal tubules have been shown to produce dopamine (DA) from (-)-3-(3,4-dihydroxyphenyl)-L-alanine (L-dopa) and to express DA1 dopamine (DA1) receptors linked to inhibition of sodium transport. The LLC-PK1 renal epithelial cell line expresses proximal tubule cell-like properties in vitro. Here, we sought to determine whether the LLC-PK1 cell line would be a useful model system to study dopaminergic mechanisms in vitro. LLC-PK1 cells contained high levels of aromatic L-amino acid decarboxylase (AADC) (Km 0.19 +/- 0.08 mM, Vmax 3.69 +/- 0.57 nmol.mg-1.min-1) and converted L-dopa to DA in a nonsaturable fashion up to 1 mM L-dopa. DA production was blocked by the AADC inhibitor carbidopa. Dopamine stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in LLC-PK1 cells in a dose-dependent manner (50% effective concentration, 1.53 +/- 0.38 microM; maximal stimulation, 46.6 +/- 10.88 pmol/mg protein); this effect was blocked by addition of DA1-receptor antagonists. L-Dopa also stimulated cAMP accumulation, and this effect was attenuated by an equimolar concentration of carbidopa and blocked by the DA1 antagonist Sch 23390. These results indicate that LLC-PK1 cells convert L-dopa to DA, which then stimulates cAMP via a DA1 receptor coupled to activation of adenylate cyclase. Moreover, the demonstration that locally formed DA can act as an autocrine/paracrine substance in LLC-PK1 cells in vitro is consistent with a role for DA as an autocrine/paracrine substance in vivo.
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PMID:Locally formed dopamine stimulates cAMP accumulation in LLC-PK1 cells via a DA1 dopamine receptor. 164 91

Dopamine (DA), via DA-1 receptors, regulates Na+ transport in the kidneys. Dopamine is synthesized from L-DOPA in the proximal tubule and presumably secreted as an autocrine/paracrine substance to stimulate DA-1 receptors localized on proximal tubular cells. We have previously reported the presence of DA-1 receptors in renal cortical homogenates and on the isolated proximal tubule of the rat and rabbit, consistent with the dopamine autocrine/paracrine model. We have localized DA-1 receptors in the proximal straight tubule of the rabbit, and in the cortical collecting duct of the rabbit and rat, but not in the distal collecting tubule or the cortical thick ascending loop of Henle. The presence of functional DA-1 receptors has been substantiated by the coexistence of DA-1 agonist-stimulated adenylate cyclase activity in the same nephron segments in which DA-r receptors have been found. Increased concentrations of intrarenal dopamine induced by dopamine-beta-hydroxylase inhibition with SKF-102698 caused a down regulation of proximal tubular DA-1 receptors and almost complete ablation of DA-1 agonist stimulated adenylate cyclase activity. Thus, dopamine may play a role in the regulation of DA-1 receptors and their linkage with adenylate cyclase. Since alterations in the renal dopaminergic system have been measured in some forms of experimental hypertension, we studied DA-1 receptors and their coupling to adenylate cyclase in the spontaneously hypertensive rat (SHR).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A renal dopamine-1 receptor defect in two genetic models of hypertension. 197 47

Repeated administration of L-dihydroxyphenylalanine (L-dopa) to rats lesioned with monolateral intranigral injections of 6-hydroxydopamine counteracted the increased density of striatal [3H]spiroperidol binding sites induced by the lesion. On the contrary, the treatment with L-DOPA further enhanced the hypersensitivity of adenylate cyclase to dopamine stimulation that follows striatal denervation. In addition, the apomorphine-induced rotations were strongly potentiated. The latter effect was antagonized by morphine given acutely shortly before the dopamine agonist. On the other hand, the efficacy of [D-Ala2]-methionine enkephalinamide to inhibit striatal adenylate cyclase was decreased in 6-hydroxydopamine-lesioned rats chronically treated with L-dopa. Moreover, in these animals, when naltrexone was given chronically together with L-dopa, the supersensitivity of the enzyme to dopamine stimulation did not develop. Finally, in 6-hydroxydopamine-lesioned rats, chronic morphine, similarly to L-dopa, further enhanced the responses of adenylate cyclase to dopamine stimulation. These data suggest that prolonged indirect activation of striatal opiate receptors and their consequent desensitization could be among the causes of the hyperactivity of D-1 dopamine receptors that follows chronic L-dopa treatment.
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PMID:Role of opiates in striatal D-1 dopamine receptor supersensitivity induced by chronic L-dopa treatment. 216 53


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