Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diurnal cycles in physical parameters in the environment modulate biochemical and physiological circadian rhythms in experimental animals, including cycles in the sensitivity to external influences. Environmental lighting synchronizes cycles of indole metabolism and melatonin synthesis in the rat pineal gland by modulating the activity of postganglionic sympathetic nerves. As a consequence, the sensitivity of pineal N-acetyltransferase to stimulation by isoproterenol or by dibutyryl cyclic AMP varies diurnally. Also, the capacity of actinomycin D to inhibit this induction varies with circadian periodicity. The cycles in sensitivity to isoproterenol reflect cycles in the system that regulates cyclic AMP production, and include variation in the availability of specific B-adrenergic binding sites, and in the sensitivity of receptor-coupled adenylate cyclase to catecholamines. Further, a variation in the response to dibutyryl cyclic AMP indicates in addition the participation of intracellular controls in the regulation of the sensitivity of N-acetyltransferase to catecholamines. The varying sensitivity to actinomycin D suggests a changing requirement for the synthesis of RNA as a function of prior environmental lighting conditions. The basic nature of these sensitivity changes suggests that diurnal cycles of environmental lighting may similarly affect other systems.
 ...
PMID:Influence of diurnal cycles on biochemical parameters of drug sensitivity: the pineal gland as a model. 0 41

An overview of the biochemical events that occur when postsynaptic pineal beta-adrenergic receptors are stimulated is presented. Emphasis is placed on the importance of the adenylate cyclase system for the induction of N-acetyltransferase (NAT). Super- and subsensitive responses of NAT to receptor agonists are related to cAMP concentration, adenylate cyclase and phosphodiesterase activities and receptor binding sites.
 ...
PMID:Studies on the control of pineal indole synthesis: cyclic nucleotides, adenylate cyclase and phosphodiesterase. 3 99

Addition of choleragen to rat pineal organ cultures caused a long-lasting stimulation of adenylate cyclase activity, and this was followed by increases in seroton N-acetyltransferase and cyclic adenosine monophosphate phosphodiesterase activities. These effects of choleragen were not blocked by the beta-adrenoceptor antagonist propranolol, but the increases in cyclic adenosine monophosphate phosphodiesterase and serotonin N-acetyltransferase activities could be prevented by the protein synthesis inhibitor cycloheximide. The results indicate that cholera toxin can mimic the induction of pineal enzymes that normally follows beta-adrenoceptor activation and suggest that increased cyclic adenosine monophosphate is a necessary and sufficient signal for such changes in enzyme activity.
 ...
PMID:Cholera toxin induces pineal enzymes in culture. 17 53

Chlordimeform is a relatively new acaricide/insecticide, whose mode of action we have investigated. It appears to interfere with amine-mediated control of nervous and endocrine systems in a variety of ways. Specifically, chlordimeform causes a build-up of the amines 5-hydroxytryptamine and to a lesser extent norepinephrine in the rat brain in vivo, antagonizes the in vivo action of reserpine in the rat (reserpine depletes amine stores in the CNS), inhibits monoamine oxidase from rat liver in vitro, and causes hypotension in rabbits. In the American cockroach it directly stimulates the heart in situ, acts synergistically with tryptamine in vivo, inhibits amine-N-acetyltransferase from cockroach head in vitro, causes accumulation of indolamines in cockroaches in vivo, and blocks the stimulation of adenylate cyclase by octopamine in the cockroach CNS in situ. It also inhibits tryptamine metabolism in whole mites in vitro.
 ...
PMID:Biochemical and physiological effects of chlordimeform. 97 27

The properties of the beta-adrenergic receptor which regulates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing)8 EC 4.6.1.1] in the pineal gland are similar to the properties of the sites which specifically bind l-[3H]alprenolol, a potent beta-adrenergic antagonist. Stimulation of the beta-adrenergic receptor results in a 30-fold increase in the activity of N-acetyltransferase (= arylamine acetyltransferase; acetyl CoA:arylamine N-acetyltransferase, EC 2.3.1.5), an enzyme involved in the synthesis of thepineal hormone melatonin. In the normal diurnal light-dark cycle there is greater physiological stimulation of the beta-adrenergic receptor in the pineal during the night than during the day. Pineals from rats kept in constant light for 24 hr possess more hormone-sensitive adenylate cyclase and specifically bind more l-[3H]alprenolol than do pineals from rats kept in the dark overnight. When rats, exposed to light for 24 hr, are treated with the beat-adrenergic agonist isoproterenol, there is a rapid loss of both hormone-sensitive adenylate cyclase activity and specific l-[3H]alprenolol binding sites. There is no change in the affinity of adenylate cyclase for isoproterenol or for its substrate, ATP. Similarly, although there are fewer binding sites, there is no change in the affinity of the remaining sites for either agonist or antagonist. Inhibition of protein synthesis with cycloheximide does not affect the loss of either adenylate cyclase activity or specific binding sites. The data suggest that stimulation of the beta-adrenergic receptor causes a rapid decrease in the number of available receptors and in hormone-sensitive adenylate cyclase activity; conversely, lack of stimulation causes an increase in these parameters. It is suggested that these changes contribute to the phenomena of super- and subsensitivity in the pineal gland by regulating the capacity of the pineal to synthesize cyclic AMP in response to beta-adrenergic stimulation.
 ...
PMID:Rapid changes in rat pineal beta-adrenergic receptor: alterations in l-(3H)alprenolol binding and adenylate cyclase. 105 61

The in vivo effects of GABA-ergic drugs on the activity of serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), two enzymes involved in melatonin biosynthesis, were investigated in light-exposed chicken retina. The ip administration of muscimol and baclofen (direct agonists of GABA-A and GABA-B receptors, respectively), aminooxyacetic acid (an inhibitor of GABA transaminase), and nipecotic acid (an inhibitor of GABA reuptake), significantly increased the retinal NAT activity by 50-100%. Similar rises in NAT activity were observed following intraocular treatment of ether-anesthetized chickens with muscimol, baclofen and GABA. In contrast to NAT, there was no effect of the tested drugs on the retinal HIOMT activity. Aminophylline (a phosphodiesterase inhibitor) markedly elevated the retinal NAT activity, and a combined treatment with the GABA-ergic drugs and aminophylline resulted in additive effects. The actions of both muscimol and baclofen were antagonized by picrotoxin and bicuculline (two GABA-A receptor blockers), whereas the effect of baclofen was not changed by a selective GABA-B receptor blocker, CGP 35,348. Melatonin given ip significantly raised NAT activity, and its combination with muscimol further stimulated the enzyme. Picrotoxin and bicuculline given to chickens during the dark phase of 12 h light--12 h dark illumination cycle significantly suppressed the nocturnal NAT activity in retina. Neither GABA nor muscimol and baclofen significantly affected basal and forskolin (1 microM)-stimulated adenylate cyclase activity in vitro in light-exposed chicken retina. It is concluded that a GABA signal (acting through type A of GABA receptors) plays an important role in a complex mechanism regulating the rhythmic melatonin biosynthesis in vertebrate retina.
 ...
PMID:The role of GABA-ergic signal in the regulation of melatonin biosynthesis in vertebrate retina. 130 60

The molecular mechanism underlying the role of calcium influx in the regulation of retinal serotonin N-acetyltransferase (NAT) activity was studied in vivo in chickens. Systemic administration of organic antagonists of voltage-sensitive calcium channels (VSCC), i.e., nimodipine and nifedipine, resulted in a marked suppression of the nocturnal increase of NAT activity in chicken retina. In contrast, NAT activity stimulated by nonhydrolysable analogs of cyclic AMP (dibutyryl-cyclic AMP and 8-bromo-cyclic AMP), forskolin, a direct activator of adenylate cyclase, and by phosphodiesterase inhibitors (aminophylline and 3-isobutyl-1-methylxanthine), was not significantly affected by various tested VSCC antagonists. The inhibitory effect of nimodipine on the dark-dependent increase in NAT activity of chicken retina was abolished by Bay K 8644, a selective VSCC agonist. The results presented in this paper indicate an important role of calcium influx through L-type of VSCC in the induction of NAT activity in chicken retina, and suggest that a requirement of calcium ions in the process of NAT induction in the retina may be primarily at the level of cyclic AMP production.
 ...
PMID:Calcium channel blockers in vivo inhibit serotonin N-acetyltransferase (NAT) activity in chicken retina stimulated by darkness and not by agents elevating intracellular cyclic AMP level. 133 45

A role of D2-dopaminergic neurotransmission in the regulation of melatonin biosynthesis in retina was studied in vivo in chickens. The nighttime rise in serotonin N-acetyltransferase (NAT)--the penultimate and key regulatory melatonin-synthesizing enzyme--was potently inhibited by both acute light exposure and agonists of dopamine D2-receptor (quinpirole, bromocriptine, and apomorphine). Spiroperidol, a selective dopamine D2-receptor blocker, increased the enzyme activity in light-exposed chickens, but had no effect in animals kept in darkness. Inhibitors of cyclic nucleotide phosphodiesterase, aminophylline, and 3-isobutyl-1-methylxanthine given peripherally, along with a direct adenylate cyclase activator forskolin injected directly into the eye, mimicked the action of darkness, and markedly enhanced the retinal NAT activity when administered to animals maintained in an illuminated environment. Dopamine D2-receptor agonists had no effect on aminophylline-stimulated enzyme activity, whereas spiroperidol enhanced it. Forskolin-driven NAT activity was suppressed by quinpirole. Spiroperidol and aminophylline given alone at different times of day under light conditions stimulated NAT activity, and their effects were mainly additive when given in combination. SCH 23390, a selective D1-dopamine receptor antagonist, did not affect the rise in NAT activity of chicken retina produced by either darkness or by aminophylline. The results provide further evidence that dopamine, acting via D2-receptors, mediates the inhibitory effects of light on the cyclic AMP-dependent dark-evoked induction of NAT activity in chicken retina.
 ...
PMID:Serotonin N-acetyltransferase activity in chicken retina: in vivo effects of phosphodiesterase inhibitors, forskolin, and drugs affecting dopamine receptors. 168 20

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.
 ...
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.
 ...
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


1 2 3 Next >>