Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The s.c. administration of 150mg L-dihydroxphyenylalaine/kg b.w. 15 min before the decapitation prevents the light induced decrease in nocturnal serotonin N-acetyltransferase activity in the rat pineal gland. The s.c. administration of 50mg imipramine/kg b.w., resp. 100mg/kg b.w., 15 min before the decapitation, slows down, or prevents the light induced fall in the activity. The maintenance of a sufficient level of active norepinephrine on beta-receptors, either by displacement of norepinephrine in the nerve endings by dopamine, or by the inhibition of norepinephrine reuptake by imipramine, thus slows down or prevents the decrease in serotonin N-acetyltransferase activity after exposure to light during the night. The i.p. administration of a phosphodiesterase inhibitor coffeine citrate in a dose 200mg/kg 90 min after switching off the light for the night stimulated serotonin N-acetyltransferase activity 270 min after the light and been switched off, but did not influence the abrupt decrease induced in nocturnal activity by exposure to light.
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PMID:Effect of dihydroxyphenylalanine, imipramine and coffeine on the light induced decrease in nocturnal serotonin N-acetyltransferase in the rat pineal gland. 13 61

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.
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PMID:Cholera toxin induces pineal enzymes in culture. 17 53

In retinas and pineal glands of rat, rabbit and hen, activities of the penultimate (and key regulatory) enzyme in melatonin biosynthesis, serotonin N-acetyltransferase (NAT), display distinct diurnal variations, with high and low values during dark and light phase of a 12-h dark: 12-h light illumination cycle. Two-hour incubation (during daytime hours in light) of isolated pineal glands of the studied vertebrates, or the retinas, with 50 microM forskolin (plus 100 microM 3-isobutyl-1-methylxanthine, IBMX-a phosphodiesterase inhibitor), and 1 mM dibutyryl-cAMP, markedly increased the tissue NAT activity. The same procedures significantly enhanced the enzyme activity of rat retina in light, however, only during nighttime hours. The forskolin (+ IBMX)-induced increase of NAT activity in rat retina was significantly lower in a calcium-free medium, and substantially enhanced when calcium concentration was raised from 1.3 mM to 3.9 mM. Treatment of rats with IBMX or aminophylline, and rabbits with aminophylline, increased NAT activity in their pineal glands irrespective of the time of the day, whereas both phosphodiesterase inhibitors significantly increased the enzyme activity of rat retina only when injected during the subjective dark hours. It is concluded that, by analogy to vertebrate pineal gland, in vertebrate retina an increase of NAT activity (and consequently melatonin formation), stimulated both physiologically (i. e. at night), or pharmacologically, involves a cAMP- and calcium dependent process of the enzyme induction.
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PMID:Serotonin N-acetyltransferase (NAT) induction in mammalian retina: role of cyclic AMP and calcium ions. 128 Feb 31

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.
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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.
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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

The possible role of dopamine in the light-induced suppression of serotonin N-acetyltransferase (NAT) activity in retinas of the African clawed frog (Xenopus laevis) was investigated using an in vitro eye cup preparation. The nocturnal increase of retinal NAT activity was significantly inhibited by either light exposure or exogenous dopamine. Spiperone, a dopamine receptor blocker, antagonized this inhibitory effect of light on NAT activity, but had no effect in darkness. The effect of spiperone required the presence of cyclic nucleotide phosphodiesterase inhibitors, 3-isobutylmethylxanthine (IBMX), papaverine, or Ro 20-1724. Under the conditions employed in this study, neither spiperone nor the phosphodiesterase inhibitors significantly affected NAT activity when added alone. This observation suggests a synergistic interaction between the dopaminergic antagonists and the phosphodiesterase inhibitors. Other dopamine receptor blockers, including haloperidol, cis-flupenthixol, clozapine and metoclopramide, increased NAT activity of light-exposed retinas incubated in the presence of IBMX. SCH 23390, a D1-selective dopamine receptor antagonist, did not increase NAT activity, nor did the alpha- and beta-adrenergic receptor antagonists tested. The effect of spiperone and IBMX on NAT activity was blocked by apomorphine and by the D2-dopamine receptor agonist LY 171555, but not by the D1-receptor agonist SKF 38393-A. The concentration of 3,4-dihydroxyphenylacetic acid was higher in light-exposed retinas than in dark-adapted retinas, suggesting that light exposure increases dopamine metabolism in Xenopus retina. The results presented in this paper suggest that dopamine, released in response to light exposure and acting on D2-dopamine receptors, is partially responsible for the light-induced suppression of the nocturnal increase in retinal NAT activity.
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PMID:Dopamine mediates the light-evoked suppression of serotonin N-acetyltransferase activity in retina. 244 15

Levels of cGMP phosphodiesterase, guanylate cyclase, and GTPase activities were determined in homogenates of chick pineal glands. Only small variations in vivo were observed with glands removed at different times of the day from birds under a standard cycle of illumination. Glands cultured under the cycle of illumination from late in the photoperiod showed a progressive loss of about half the phosphodiesterase activity in 24 h, and an increase of roughly 75% in GTPase activity within 12 h. No simple correlations were found between variations in levels of enzyme activity and the diurnal cycles in pineal content of cGMP and level of serotonin N-acetyltransferase (NAT) activity. However, onset of rapid increases in 3',5'-cyclic GMP (cGMP) content and NAT activity was correlated with a transient decrease of about 30% in the phosphodiesterase activity, both in vivo and in culture. Further, known inhibitors of phosphodiesterase activity previously shown to elicit increase of cGMP content and marked elevation of NAT activity in cultured glands only inhibited phosphodiesterase activity of homogenates by 25-30%. It was therefore concluded that the transient decrease in level of phosphodiesterase may facilitate onset of increase in pineal cGMP content. However, it seems improbable that changes in pineal content of enzymes of guanine nucleotide metabolism are essential to regulation of diurnal cycles in cGMP content or level of NAT activity.
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PMID:Enzymes of guanine nucleotide metabolism and the diurnal cycle in cGMP content of the chick pineal gland. 613 5

The light/dark cycle influences the rhythmic production of melatonin by the trout pineal organ through a modulation of the serotonin N-acetyltransferase (NAT) activity. In static organ culture, cyclic AMP (cAMP) levels (in darkness) and NAT activity (in darkness or light) were stimulated in the presence of forskolin, isobutylmethylxanthine, or theophylline. Analogues of cAMP, but not of cyclic GMP, induced an increase in NAT activity. Light, applied after dark adaptation, inhibited NAT activity. This inhibitory effect was partially prevented in the presence of drugs stimulating cAMP accumulation. In addition, cAMP accumulation and NAT activity increase, induced by forskolin, were temperature dependent. Finally, melatonin release, determined in superfused organs under normal conditions of illumination, was stimulated during the light period of a light/dark cycle by adding an analogue of cAMP or a phosphodiesterase inhibitor. However, no further increase in melatonin release was observed during the dark phase of this cycle in the presence of the drugs. This report shows for the first time that cAMP is a candidate as intracellular second messenger participating in the control of NAT activity and melatonin production by light and temperature.
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PMID:Regulation of melatonin production by pineal photoreceptor cells: role of cyclic nucleotides in the trout (Oncorhynchus mykiss). 839 May 63

Caffeine, an important member of methylxanthines, induced a prolonged nocturnal rise in pineal melatonin content and an increase in its rate-limiting enzyme serotonin N-acetyltransferase (NAT) activity. The highest levels were reached five hours after subcutaneous caffeine injection to male rats in the dark phase, where the NAT activity increased from 920+/-70 pM/pineal/h in the control group to 1190+/-120 pM/pineal/h (P<0.001) in the treated group. The pineal melatonin content, as well, was elevated from 520+/-40 pg/pineal in the control group to 1120+/-80 pg/pineal (P<0.001) in caffeine treated group. These changes could be attributed to the depressive effect of caffeine on the activity of phosphodiesterase (PDE), the enzyme responsible for the hydrolysis of the intracellular second messenger cyclic adenosine monophosphate (cAMP).
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PMID:CAFFEINE INJECTION IN THE DARK PHASE PROLONGS THE NOCTURNAL RISE IN SEROTONIN N-ACETYLTRANSFERASE ACTIVITY AND MELATONIN CONTENT IN THE PINEAL GLAND OF MALE RATS. 1046 35

The chick pineal gland rhythmically synthesizes two 5-methoxyindoles, melatonin and 5-methoxytryptophol. These rhythms are circadian in nature and have opposite phases. The aim of this study was to determine the effects of cycloheximide, a protein synthesis inhibitor, and aminophylline, an inhibitor of phosphodiesterase, on 5-methoxytryptophol content in the chick pineal gland and to compare this with the drugs' action on pineal melatonin production. Inhibition of melatonin biosynthesis by cycloheximide (1 mg/kg, i.p. ), revealed by a marked reduction in the nighttime activity of serotonin N-acetyltransferase (AA-NAT; a key regulatory enzyme in melatonin synthesis) and melatonin concentrations, was accompanied by a significant increase in 5-methoxytryptophol content. In contrast, administration of aminophylline (100 mg/kg, i.p.) to light-exposed chicks significantly increased pineal AA-NAT activity and melatonin levels and decreased 5-methoxytryptophol concentrations. It is concluded that in the chick the production of pineal 5-methoxytryptophol and melatonin is inversely correlated.
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PMID:Effects of cycloheximide and aminophylline on 5-methoxytryptophol and melatonin contents in the chick pineal gland. 1107 32


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