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)

The activity of serotonin N-acetyltransferase (NAT), a key regulatory enzyme in the melatonin biosynthetic pathway, was examined in low-density monolayer cultures of chick embryo retinal cells prepared with three levels of photoreceptor enrichment. In cultures prepared from embryonic day 8 retinas (E8), photoreceptors represented approximately 30% of the total cell population, whereas in those prepared from embryonic day 6 retinas (E6), approximately 70% of the cells were photoreceptors. In E8 retinas treated with kainic acid to destroy neurons (E8K), the relative content of photoreceptors was increased to approximately 50%. NAT activity was detectable in the cultures under all conditions studied, and was markedly increased by drugs that increase intracellular cyclic AMP levels and cyclic AMP-dependent protein kinase activity: 8-bromocyclic AMP, forskolin, and 3-isobutyl-1-methylxanthine (IBMX). Consistent with the hypothesis that NAT is localized in photoreceptors, the effects of the stimulatory treatments were significantly greater in E6 and E8K cultures than in E8 cultures. The stimulation of NAT activity in E6 cultures was inhibited by actinomycin D and cycloheximide, suggesting the involvement of RNA and protein synthesis. Dopamine inhibited the induction of NAT activity by forskolin and IBMX, but not that elicited by 8-bromocyclic AMP. The dopamine-mediated suppression of activity was significantly inhibited by pertussis toxin and by spiperone and sulpiride, both D2-dopamine receptor antagonists, but not by SCH 23390, a D1-dopamine receptor blocker, or antagonists of alpha-adrenergic, beta-adrenergic, or serotonergic receptors. Because the inhibitory effect of dopamine on E6 and E8K cultures was at least as great as that on E8 cultures, the results suggest that dopamine acts on D2-like receptors on photoreceptors. The receptors appear to be coupled to adenylate cyclase through an inhibitory GTP-binding protein and to mediate inhibition of cyclic AMP synthesis and consequent induction of NAT activity.
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PMID:Cyclic AMP-dependent induction of serotonin N-acetyltransferase activity in photoreceptor-enriched chick retinal cell cultures: characterization and inhibition by dopamine. 169 44

In vivo melatonin production was stimulated during the daytime in pineal glands of female Syrian hamsters following the administration of several injections of either isoproterenol, a beta-receptor agonist, or forskolin, an adenylate cyclase stimulator. The large increase in melatonin following either isoproterenol or forskolin administration was not accompanied by significant changes in N-acetyltransferase (NAT) activity. The results suggest that the Syrian hamster pineal gland, as in other species, responds by producing melatonin during the light phase if the stimulus is adjusted to its particular and specific regulatory mechanisms, i.e., if beta-adrenergic stimulation is continued for 4-8 h. The lack of a commensurate increase in NAT activity raises the question of the need of maximal enzymatic activity for a significant rise in melatonin production in the Syrian hamster pineal gland.
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PMID:In vivo administration of isoproterenol or forskolin during the light phase induces increases in the melatonin content of the Syrian hamster pineal gland without a rise in N-acetyltransferase activity. 215 23

The type of catecholamine receptor involved in the regulation of serotonin N-acetyltransferase (NAT) activity and melatonin (N-acetyl-5-methoxytryptamine) level in chicken retina was compared to that regulating these parameters in the pineal gland. Systemic administration of apomorphine, a dopamine receptor agonist, resulted in marked inhibition of the nocturnal increase of retinal NAT activity and melatonin content. Apomorphine did not affect NAT activity or melatonin content of the pineal gland. In contrast, clonidine, an alpha-2 adrenergic receptor agonist, inhibited the nocturnal rise in pineal NAT activity and melatonin content although being without effect on these parameters in retina. Apomorphine-induced inhibition of retinal NAT activity was blocked by spiperone, a D2-dopamine receptor antagonist, but not by antagonists of D1-dopamine, alpha-1, alpha-2 and beta adrenergic receptors. Systemic or intraocular injection of quinpirole, a D2-dopamine receptor agonist, in the middle of the dark phase of the light-dark cycle markedly reduced retinal NAT activity and melatonin level, whereas injections of SKF 38393-A, a D1-dopaminergic agonist, had no effect. The inhibitory effect of clonidine on pineal NAT activity was blocked by yohimbine, an alpha-2 adrenergic receptor antagonist. The results presented in this paper demonstrate that NAT activity and melatonin content in chicken retina and pineal gland are differentially modulated in vivo by D2-dopamine and alpha-2 adrenergic receptors, respectively. Despite the different types of receptors involved, both tissues may share a common pathway for catecholamine-mediated inhibition of melatonin biosynthesis, i.e., inhibition of adenylate cyclase activity.
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PMID:Catecholamine receptors regulating serotonin N-acetyltransferase activity and melatonin content of chicken retina and pineal gland: D2-dopamine receptors in retina and alpha-2 adrenergic receptors in pineal gland. 256 81

It has been suggested that the HIV virus binds to VIP recognition sites which can be blocked by the octapeptide, peptide T. Stimulation of VIP receptors on pinealocytes activates adenylate cyclase and increases the activity of the enzyme serotonin N-acetyltransferase (NAT). We examined whether peptide T or D-Ala peptide T amide affected this induction. We found no evidence for peptide T interference with NAT induction and conclude that if peptide T inhibits attachment of HIV virus to VIP receptors, it does so at regions other than that occupied by VIP in stimulating adenylate cyclase and NAT.
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PMID:Peptide T does not affect induction of pineal N-acetyltransferase by vasoactive intestinal peptide. 271 84

In the chicken pineal gland, norepinephrine, released at sympathetic nerve endings, plays a role in synchronizing the circadian rhythm of melatonin synthesis. This effect appears to be exerted via an adrenergic inhibition of arylalkylamine N-acetyltransferase, the melatonin rhythm-generating enzyme. The present study indicates that the nighttime peak of N-acetyltransferase activity developed by organ-cultured chick pineal glands is inhibited by adrenergic agonists with a potency order characterizing alpha 2-adrenergic receptors: UK 14,304 greater than clonidine greater than alpha-methylnorepinephrine = epinephrine greater than cirazoline greater than phenylephrine greater than isoproterenol. The mechanism of this alpha 2-adrenergic response was further analyzed in organ cultures, by studying the ability of clonidine to block the cyclic AMP-dependent and the depolarization-dependent stimulations of N-acetyltransferase activity. Clonidine prevented the rise in N-acetyltransferase activity evoked by the adenylate cyclase activators forskolin and cholera toxin or by the phosphodiesterase inhibitor Ro 20,1724. The stimulatory effect of dibutyryl cyclic AMP was also blocked by clonidine. Activation of pineal alpha 2-adrenergic receptors effectively prevented the stimulation of N-acetyltransferase by depolarizing concentrations of KCl. The possibility that the alpha 2-adrenergic effect might be exerted at a step distal to cyclic AMP production is discussed.
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PMID:Alpha 2-adrenergic regulation of arylalkylamine N-acetyltransferase in organ-cultured chick pineal gland: characterization with agonists and modulation of experimentally stimulated enzyme activity. 288 97

The exposure of organ cultured pineal glands of Syrian hamsters to forskolin, an adenylate cyclase activator, caused marked increases in serotonin N-acetyltransferase activity and melatonin content in a dose-related manner (1-100 microM) when glands were collected in the second half of the dark period. However, addition of forskolin to glands collected anytime during the light period or at the beginning of the dark period failed or only modestly stimulated either pineal N-acetyltransferase activity or melatonin levels. Similar results were obtained with isoproterenol. The results suggest that intrapinealocyte regulatory mechanisms may determine the nocturnal rise in the Syrian hamster pineal gland.
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PMID:Forskolin, an activator of adenylate cyclase activity, promotes large increases in N-acetyl transferase activity and melatonin production in the Syrian hamster pineal gland only during the late dark period. 341 80

Pineal N-acetyltransferase (NAT) is activated by increased sympathetic activity or by administration of isoproterenol. These experiments examined the effects of fetal alcohol exposure on the pharmacological induction of NAT activity in rats. Fetal alcohol exposure resulted in a significant reduction of NAT activity compared to that in rats whose mothers received a nutritionally controlled liquid diet or a laboratory chow diet during gestation. Stimulation of NAT activity in vitro by forskolin, which directly stimulates adenylate cyclase, also was significantly less in pineal glands from fetal alcohol exposed rats when compared with pineal NAT activity from rats exposed to the control diets during gestation. The results suggest that the effects of fetal alcohol exposure is not limited to the beta-adrenergic receptor at the cell membrane, but that exposure to alcohol in utero may result in more general effects on intracellular mechanisms involved in pineal NAT enzyme synthesis or activity.
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PMID:Reduction of rat pineal N-acetyltransferase activity by fetal alcohol exposure. 342 19

1. In pineal glands of adult spontaneously hypertensive rats (Okamoto strain), dopamine levels increased 34%, adrenaline concentrations increased 152% and noradrenaline levels decreased by 26%, when compared with Wistar-Kyoto normotensive controls. 2. These results are consistent with the hypothesis of an increased uptake of peripheral adrenaline resulting in increased release of noradrenaline from pineal sympathetic nerves in hypertensive rats. 3. The activity of pineal N-acetyltransferase was increased fourfold in hypertensive rats, indicating increased stimulation of pineal beta-adrenoreceptors. 4. Methylation of pineal membrane phospholipids was also increased (100-320%) in hypertensive rats. 5. These results indicate a correlation in vivo between increased beta-adrenoreceptor stimulation and increased methylation of membrane phospholipids in the rat pineal gland, which could result in changes in membrane fluidity and affect the coupling of the beta-adrenoreceptors to the adenylate cyclase.
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PMID:Increased adrenaline, beta-adrenoreceptor stimulation and phospholipid methylation in pineal gland of spontaneously hypertensive rats. 625 15

The effects of active immunization against a range of gonadal steroids on pineal beta-adrenoceptors were studied in cycling Merino ewes. In selected cases, the effects of exogenous steroids were also investigated. Immunization against progesterone had no detectable effect on pineal beta-adrenoceptor density or ligand binding affinity. Immunization against estrone or 17 beta-estradiol significantly increased binding affinity and decreased beta-receptor density. Testosterone immunization in ewes caused similar effects but to a lesser degree. In contrast, immunization against androstenedione resulted in a decreased affinity and an increase in receptor density in ewes. In subsequent experiments, some parameters of pineal function in intact cycling and ovariectomized ewes were compared; a significant decrease in beta-receptor density and an increase in binding affinity were noted in the ovariectomized animals. Androstenedione-releasing implants decreased beta-receptor density and increased beta-receptor affinity in pineals from intact ewes, but these implants had no effect on pineal parameters in ovariectomized ewes. Immunization of ewes against 17 beta-estradiol had no significant effects on basal or isoprenaline-stimulated N-acetyltransferase or adenyl cyclase activities. Immunization of ewes against melatonin, or in vitro incubation of pineal glands with the hormone had no effects on the pineal parameters studied. It is concluded that estrogens affect the pinealocyte beta-receptors in ewes, while specific androgens may act indirectly on these receptors to modify their interaction with estrogens.
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PMID:Modification of sheep pineal beta-adrenoceptors by some gonadal steroids but not by melatonin. 631 89

To clarify the role and site of action of gamma-aminobutyric acid (GABA) in ovine pineal glands, we have investigated the effects of aminooxyacetic acid (AOAA), an inhibitor of GABA transaminase, on endogenous GABA content and beta-adrenoceptor mediated pineal function in Merino sheep. A significant elevation of endogenous GABA levels was noted in the glands, but no effect was observed on radioligand binding in vitro to pineal beta-adrenoceptors following in vivo administration of AOAA. Incubation of washed pineal membranes with GABA or AOAA had no effect on ligand binding to beta-adrenoceptors. Incubation of Merino pineal slices with GABA inhibited isoprenaline-stimulated but not basal serotonin N-acetyltransferase (NAT) activity. Incubation of whole pineal homogenates with GABA was without effect on either isoprenaline-stimulated or basal adenyl cyclase activity. Thus, Merino pineal glands resemble bovine pineals in that beta-adrenoceptor mediated melatonin biosynthesis in both species may be regulated in part by GABA. Our results indicate that GABA may exert its effect on Merino pineal NAT activity at a locus distal to the site of action of adenyl cyclase; however, the detailed mechanism and physiological role of this regulation remain to be elucidated.
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PMID:Sheep pineal beta-adrenoceptor function--interaction with gamma-aminobutyric acid. 632 80


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