Jolanta Rosiak

Daily variation in the concentration of melatonin and 5-methoxytryptophol in the goose pineal gland, retina, and plasma.

The goose pineal gland rhythmically produces two 5-methoxyindole compounds, namely melatonin and 5-methoxytryptophol. Melatonin concentrations were high at night and low during the day, while in contrast 5-methoxytryptophol levels were markedly higher during the day compared to the night-time values. Rhythmic oscillations in melatonin content, with high night-time values, have also been found in plasma and the retina of goose. The pineal and retinal melatonin rhythm mirrored oscillations in the activity of serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in the melatonin biosynthetic pathway). Acute exposure of geese to light at night markedly decreased melatonin levels in the pineal, plasma, and retina. In addition, this light exposure resulted in a significant increase in pineal 5-methoxytryptophol content. Our results demonstrate, for the first time, the ability of the goose pineal gland and retina to synthesise melatonin and 5-methoxytryptophol in a rhythmic manner.

Suppression of melatonin biosynthesis in the chicken pineal gland by retinally perceived light - involvement of D1-dopamine receptors.

Abstract:  In this study the role of retinal dopamine (DA) receptors in the light‐induced suppression of melatonin biosynthesis in the chicken pineal gland was examined. Exposure of dark‐adapted chickens to low intensity light (4 lux) at night significantly decreased the activity of serotonin N‐acetyltransferase (AA‐NAT; the penultimate and key regulatory enzyme in melatonin production) and melatonin content in the pineal gland. This suppressive action of light was blocked by intraocular (i.oc.) administration of SCH 23390 (a selective antagonist of D1‐DA receptors), but was not affected by sulpiride (a selective antagonist of D2‐DA receptors). Injection of DA (i.oc.) to dark‐adapted chickens significantly decreased pineal AA‐NAT activity and melatonin content in a dose‐ and time‐dependent manner. The action of DA was mimicked by selective agonists of D1‐DA receptors, SKF 38393 and SKF 81297, and non‐hydrolyzable analogs of cyclic AMP (cAMP), dibutyryl‐cAMP and 8‐bromo‐cAMP. However, i.oc. administration of quinpirole, a selective agonist of D2‐DA receptors, did not modify pineal AA‐NAT activity. In contrast, quinpirole potently decreased nocturnal AA‐NAT activity in the retina. Systemic administration of SCH 23390 to chickens blocked the i.oc. DA‐evoked decline in nighttime pineal AA‐NAT activity, whereas sulpiride was ineffective. These findings indicate that light activation of retinal dopaminergic neurotransmission, with concomitant stimulation of D1‐DA receptors positively coupled to the cAMP generating system, plays an important role in a cascade of events regulating pineal activity.

The relationship between melatonin and dopamine rhythms in the duck retina

In the retina of duck, levels of dopamine (DA) and its main metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), fluctuate throughout the day, with high values during the light phase. The rhythmic changes in DA content and metabolism are out of phase with the daily oscillations in melatonin (MEL) and serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in MEL biosynthesis) activity. Acute exposure of ducks to light at night potently increased levels of DA and DOPAC, and decreased AA-NAT activity and MEL content in the retina. Intraocular administration of MEL to light-adapted ducks produced a significant decline in retinal DA and DOPAC concentrations. On the other hand, quinpirole, a D(2)/D(4)-DA receptor agonist, administered intraocularly, markedly suppressed the night-time retinal AA-NAT activity and MEL. These findings provide, for the first time, evidence for an inverse relationship between the DA system and MEL in the duck retina.

Daily variation in the concentration of 5-methoxytryptophol and melatonin in the duck pineal gland and plasma

The duck pineal gland rhythmically produces two 5‐methoxyindole compounds, i.e. 5‐methoxytryptophol and melatonin. 5‐Methoxytryptophol levels are low at night and high during the day, while melatonin concentrations are high at night and low during the day. The melatonin rhythm reflects oscillations in the activity of serotonin N‐acetyltransferase (AA‐NAT; a penultimate and key regulatory enzyme in the melatonin biosynthetic pathway). The activity of hydroxyindole‐O‐methyltransferase (HIOMT; an enzyme involved in the synthesis of both 5‐methoxytryptophol and melatonin) does not exhibit any significant rhythmic changes throughout the 24‐hr period. Plasma levels of melatonin exhibited daily changes that were parallel to fluctuations in pineal melatonin content. Although plasma concentrations of 5‐methoxytryptophol were low in ducks, they showed daily variations. The mean 5‐methoxytryptophol concentration between zeitgeber time 9 (ZT9) and ZT15 was 2.4‐times higher than the mean value for samples collected between ZT18 and ZT3. These findings indicate that in the duck the pineal production of 5‐methoxytryptophol and melatonin may be inversely correlated.

Near-ultraviolet radiation suppresses melatonin synthesis in the chicken retina: a role of dopamine.

Effects of near-ultraviolet radiation (UV-A; 325-390 nm, peak at 365 nm) on melatonin content and activity of serotonin N-acetyltransferase (AA-NAT; a key regulatory enzyme in melatonin biosynthesis) were examined in the retina of chickens. Acute exposure of dark-adapted animals to UV-A light produced a marked decline in melatonin content and AA-NAT activity of the retina. The magnitude of the observed changes was dependent upon duration of the light pulse and age of chickens, with 1-2-week old birds being more sensitive to UV-A action than 6-7-week old ones. The decrease in the nocturnal AA-NAT activity evoked by a 5-min UV-A pulse gradually deepened during the first 30 min after the return of chickens to constant darkness, then the enzyme activity began to rise, reaching nearly complete restoration within 2.5 hr. Systemic administration to chickens of alpha-methyl-p-tyrosine (an inhibitor of catecholamine synthesis; 0.3 g/kg) blocked the suppressive effect of UV-A light on retinal AA-NAT activity. Haloperidol, sulpiride (blockers of D2-family of dopamine (DA) receptors) and 2-chloro-11-(4-methylpiperazino)dibenz[b,f]oxepin (an antagonist of D4-DA receptors), given intraocularly (1-100 nmol/eye) prevented the UV-A light-evoked decrease in AA-NAT activity in the chicken retina in a dose-dependent manner, while raclopride (300 nmol/eye), an antagonist of D2/D3-DA receptors, was ineffective. In dark-adapted chickens exposure to UV-A light increased the DA content of the retina. It is concluded that UV-A radiation, similar to visible light, potently suppresses melatonin biosynthesis in the retina of chicken, with a D4-dopaminergic signal playing the role of an intermediate in this action.

Effects of near-ultraviolet light on the nocturnal serotonin N-acetyltransferase activity of rat pineal gland

Effects of near-ultraviolet (UV-A; 325-390 nm, peak at 365 nm) light on the activity of the pineal serotonin N-acetyltransferase (NAT; a penultimate and key regulatory enzyme in melatonin biosynthesis) were examined in rats. Acute exposure of dark-adapted animals to UV-A radiation produced a marked suppression of NAT activity of the pineal gland, the effect being dependent on exposure time. The decrease in the night-time NAT activity evoked by a 1-min pulse of UV-A light (as well as by a 15-s pulse of broad-band visible light) gradually deepened during the first 40 min of treatment of animals with constant darkness, then the enzyme activity began to rise reaching control values by 3 h. Treatment of rats with a protein synthesis inhibitor, cycloheximide, attenuated this night-driven reactivation of the pineal NAT activity. The presented results provide evidence that UV-A light is a powerful signal capable of controlling melatonin biosynthesis in rat pineal gland.

Near-ultraviolet light perceived by the retina generates the signal suppressing melatonin synthesis in the chick pineal gland : an involvement of NMDA glutamate receptors

Exposure of dark-adapted chicks to near ultraviolet (UV-A) light significantly decreased melatonin (MEL) content and the activity of serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in MEL production) in the pineal glands. Significant reduction in MEL level and AA-NAT activity was also found in pineals of animals whose heads were covered with black opaque tape, an observation suggesting that in the chicken UV-A light perceived by the eyes alone is capable of affecting MEL synthesis in the pineal gland. Covering the chicks eyes, in addition to the head, totally blocked the studied UV-A action. Although SCH 23390 (a selective D1-dopamine receptor antagonist), injected directly into both eyes at a dose of 10 nmol/eye, prevented the decline in pineal AA-NAT activity produced by retinal illumination with white light, the drug did not modify the UV-A light-evoked decrease in the enzyme activity. MK-801 (a selective antagonist of NMDA glutamate receptors; 1 nmol/eye) abolished the suppressive action of UV-A light on pineal AA-NAT activity, but it was inactive in the case of white light. Intraocularly injected sulpiride and CNQX (selective antagonists of D2-dopamine and AMPA/kainite glutamate receptors, respectively) had no effect on the actions of both UV-A and white light (acting on the eyes only) on pineal AA-NAT activity. It is concluded that in the chick retinally perceived UV-A light generates a signal which suppresses MEL production in the pineal gland. At the level of the retina, such signal does not involve dopamine, but is dependent on the stimulation of NMDA glutamate receptors.

UV-A light regulation of arylalkylamine N-acetyltransferase activity in the chick pineal gland: role of cAMP and proteasomal proteolysis

Abstract:  Acute exposure of dark‐adapted, cultured chick pineal glands to UV‐A light significantly decreased the tissue cAMP concentration and the activity of arylalkylamine N‐acetyltransferase (AANAT), the penultimate and key regulatory enzyme in the melatonin biosynthetic pathway. The magnitude of these changes was dependent on the duration of UV‐A exposure. The UV‐A light‐evoked decline in pineal AANAT activity was blocked by cAMP protagonists (forskolin and dibutyryl‐cAMP) and by inhibitors of the proteasomal degradation pathway (MG‐132, proteasome inhibitor I, and lactacystin). These results indicate that the chick pineal gland is directly sensitive to UV‐A light. By analogy to white light, the suppressive action of UV‐A radiation on AANAT activity in the chick pineal gland involves changes in the tissue cAMP level and enhanced proteasomal proteolysis.

Effects of Near-Ultraviolet (UV-A) Light on Melatonin Biosynthesis in Vertebrate Pineal Gland

The effects of near-ultraviolet (UV-A) irradiation on nocturnal activity of serotonin N-acetyltransferase (NAT; a key regulatory enzyme in melatonin biosynthesis) in the pineal gland of the rat and chick were investigated. Exposure of the animals to UV-A during the 4th or 5th hour of the dark phase of the 12:12 h light-dark (LD) cycle suppressed the night-driven NAT activity in a time-dependent manner, the effects being generally more pronounced in rats than in chicks. The UV-A-evoked suppression of the nocturnal NAT activity was completely restored within 2 h (chicks) or 3 h (rats) in animals which, after irradiation, were returned to darkness. When a short UV-A pulse was applied to the animals after midnight, it induced a decrease in the enzyme activity in both species; yet, the effect was readily reversible only in chicks. The results presented here, as well as other data, demonstrate that UV-A light is a powerful signal affecting the pineal melatonin-generating system both in mammals and avians, and that the involved mechanisms may differ in the tested species.

L-745,870 suppresses the nighttime serotonin N-acetyltransferase activity in chick retina: in vivo evidence for agonist activity at D4-dopamine receptors.

Summary. This study examined the in vivo activity of L-745,870 at dopamine (DA) D4 receptors, using the chick retina as a model system. In dark-adapted retinas of various vertebrates, including hen, DA acting via D4 receptors suppresses melatonin content and activity of serotonin N-acetyltransferase (AA-NAT, a key regulatory enzyme in melatonin synthesis). Systemic administration to chicks of quinpirole (0.1 mg/kg), a high affinity agonist of D3/D4-DA receptors, potently decreased the nighttime AA-NAT activity of the retina. The quinpirole-evoked decline in the enzyme activity was attenuated by L-745,870 (0.1–10 nmol/eye). In addition to this action, L-745,870 given to chicks either directly into the eye (0.03–10 nmol/eye) or intraperitoneally (0.5–5 mg/kg) decreased the nighttime AA-NAT activity of the retina in a dose-dependent manner. The suppressive effect of L-745,870 on retinal AA-NAT activity was blocked by 2-chloro-11-(4-methylpiperazino)dibenz[b,f]oxepin, an antagonist of D4-DA receptors, but was not affected by raclopride, an antagonist of D2/D3-DA receptors. Altogether these results indicate that in chicks L-745,870, the potent putative D4-DA receptor antagonist, behaves in vivo as a partial D4 agonist.