Retinal Localization of the Hydroxyindole-O-methyl Transferase (HIOMT) in the Rat

Cardinali, Daniel P.; Rosner, Jorge M.

doi:10.1210/endo-89-1-301

Cited by 159 publications

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“…3 shows that the rhythm in retinal N-acetyltransferase activity persists after pinealectomy in both an LD cycle and in DD. (18)(19)(20)(22)(23)(24). The isolated retinae of rats (32) and trout (33) In sparrows, pinealectomy abolishes circadian rhythms of locomotor activity (34,35), and transplantation experiments have demonstrated that the pineal is a dominant circadian pacemaker (36).…”

Section: Methodsmentioning

confidence: 99%

Retinal rhythms in chicks: circadian variation in melantonin and serotonin N-acetyltransferase activity.

Hamm¹,

Menaker²

1980

Proc. Natl. Acad. Sci. U.S.A.

221

115

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There is a large-amplitude circadian rhythm of indoleamine metabolism in the retina-pigment epithelium of the chicken. N-Acetyltransferase activity (arylamine acetyltransferase; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) and melatonin content are 15-fold higher at night than during the day in a cycle of 12 hr of light and 12 hr of dark; in constant darkness there is a 4-fold increase during the subjective night. Light at midnight inactivates N-acetyltransferase and lowers melatonin. N-Acetyltransferase activity is found predominantly in the retina. The circadian rhythm of this enzyme activity persists in pinealectomized chicks. Thus the pineal is not responsible for retinal indoleamine rhythms. Retinal and pineal levels of N-acetyltransferase activity behave similarly under several conditions. In the chicken, the eye is a major site of rhythmic indoleamine metabolic activity. Many features of photoreceptor cell physiology fluctuate with daily rhythmicity. Evidence suggesting that a general feature of retinal metabolism in all vertebrate classes is its modulation by daily rhythms has accumulated rapidly (1-14). This is not surprising in cells that are exquisitely specialized for reception of light, which varies with an environmentally imposed periodicity. What is more interesting is that this rhythmicity continues even in the absence of the light-dark cycle that normally synchronizes it. In constant conditions there is endogenously rhythmic regulation of daily disc shedding of photoreceptor outer segments (1-3).Some aspects of photoreceptor metabolism that exhibit daily rhythms can be directly affected by melatonin (N-acetyl-5-methoxytryptamine) (15-17). The retina contains the enzymes necessary to make melatonin (18-21). Quay (18) has found hydroxyindole O-methyltransferase in the retina of a variety of vertebrates, including chickens. Recently Binkley et al. (21) have found a day-night change in N-acetyltransferase (arylamine acetyltransferase; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) activity in the eyes of chickens, sparrows, and rats. Serotonin is also found in the chick retina (22-24). Thus it seems possible that the retina makes melatonin. We have examined the possibility that the melatonin content of the retina, and the activity of retinal N-acetyltransferase, a controlling enzyme in melatonin synthesis, have circadian rhythms similar to their well-studied oscillations in the pineal gland. MATERIALS AND METHODSAnimals. Chicks (White Leghorn pullets, Babcock B-300 strain, Gallus domesticus) were purchased locally on the day of hatching and kept in warmed brooders with food (Purina Chick Starteena) and water available ad lib, on a light-dark cycle (LD 12:12, lights on 0000-1200 central standard time) until age 2-3 weeks. The light source was Sylvania Cool White fluorescent bulbs, which produced an intensity at the level of the brooders during the light period of 700-800 lux, measured with a Gossen Luna Pro photometer (model B650920). When light was given in the middle of the ...

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Section: Methodsmentioning

confidence: 99%

Retinal rhythms in chicks: circadian variation in melantonin and serotonin N-acetyltransferase activity.

Hamm¹,

Menaker²

1980

Proc. Natl. Acad. Sci. U.S.A.

221

115

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“…Pineal HO-IndMeTrase activity was assayed in vitro by measurement of the transfer of a [14C]_ methyl group from S-adenosylmethionine to N-acetylserotonin (10). The radioactive methylated product was identified as melatonin by thin-layer chromatography (11). Results were analyzed by analysis of variance (12).…”

Section: Methodsmentioning

confidence: 99%

Control of the Rat Pineal Gland by Light Spectra

Cardinali

Larin

Wurtman

1972

Proc. Natl. Acad. Sci. U.S.A.

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Control of pineal hydroxyindole-O-methyl transferase (S-adenosylmethionine: N-acetylserotonin-Omethyl transferase; EC 2.1.1.4) by light spectra was determined by placing groups of rats previously housed in continuous darkness under one of seven light sources for 96 hr; rats were exposed to the same intensity of irradiation. Activity of the enzyme was lowest in rats maintained under green light (X peak = 530 nm); blue and yellow light were somewhat less effective; red and ultraviolet light did not significantly lower the enzyme activity. The suppression of pineal hydroxyindole-O-methyl transferase by full-spectrum light sources could be correlated with the proportions of their spectral outputs in the blue-green-yellow range. These observations suggest that the retinal photopigment that mediates pineal responses to light in rats is rhodopsin or another compound with similar absorption properties.The pineal gland is a neuroendocrine transducer; it converts neural signals that are generated in the retina by light, and transmitted to it by postganglionic sympathetic neurons, into a hormonal output, i.e., the secretion of melatonin (1). Both the morphology and the biochemical activity of rat pineal gland exhibit a marked dependence on the light to which the animal is exposed. For example, pineals of rats kept under continuous light weigh less than those of controls (2), display lower in vitro activities of two of the enzymes involved in melatonin biosynthesis: hydroxyindole-O-methyl transferase(HO-IndMeTrase; S-adenosylmethionine: N-acetylserotonin-O-methyl transferase; EC 2.1.1.4) (3-5) and serotonin-N-acetyltransferase (EC 2.3.1.5) (6), and contain less melatonin (7).In all published studies on the photic control of thc mammalian pineal organ, researchers have manipulated the time of exposure, but have not compared the effects of spectral variations or magnitude of irradiation. Inasmuch as the retinal photoreceptors that mediate vision display characteristic action spectra, it seemed likely that the distribution of spectral power of a light source would also influence the extent to which that source modified pineal functions. By using light sources that emit radiation in specific regions of the visible and near-ultraviolet spectra, we have attempted to define in rats the magnitude of inhibition of pineal HOIndMeTrase by light spectra. Our studies suggest that the same or closely related photopigments mediate both the visual and the neuroendocrine effects of light in rats. MATERIALS AND METHODSSprague-Dawley male rats, 2-25 months old, (230-250 g) were housed in polyearbonate cages covered with screened metal lids that caused no selective interference with the light transmission from overhead luminaires. Rats were kept in an airconditioned room (20 i 2°), and given food (Big Red Lab Chow, Mother Hubbard, Lowell, Mass.) and water ad libitum.Seven experiments were performed, and seven different sets of bulbs were used (Table 1). The distribution of spectral power of the light sources was determined with a doubl...

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“…In mammals, melatonin was thought to be a hormone exclusively synthesized by the pineal gland (Axelrod et al, 1965), its function being primarily the control of circadian and circannual rhythms, including seasonal reproduction. However, the discovery of the key enzymes of melatonin synthesis, hydroxindole-O-methyltransferase (HIOMT, now called N-acetylserotonin-O-methyltransferase (ASMT) and aralkylamine-N-acetyltransferase (AANAT) in the retina (Cardinali & Rosner, 1971) and lately in many peripheral organs, tissues and fluids (see (Acuña-Castroviejo et al, 2014) for review) has accounted for the reclassification of melatonin as a multitasking molecule (Tan et al, 2003;Reiter et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Evidence of melatonin synthesis in the ram reproductive tract

et al. 2016

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SUMMARYMelatonin is a ubiquitous molecule found in a wide range of fluids, one of them being ram seminal plasma, in which it can reach higher concentrations than those found in blood, suggesting an extrapineal secretion by the reproductive tract. In order to identify the source of the melatonin found in ram seminal plasma, we first tried to determine whether the melatonin levels were maintained during the day. For this purpose, melatonin concentrations were measured in seminal plasma obtained from first ejaculates of six rams at 6:00 a.m. in total darkness, at 10:00 a.m. and at 14:00 p.m. The melatonin concentration was higher (p < 0.05) in ejaculates collected at 6:00 a.m. than at 10:00 and 14:00. There was no statistical difference between the latter. To further corroborate an extrapineal secretion of melatonin, the presence of the two key enzymes involved in melatonin synthesis, arylalkylamine-N-acetyltransferase (AANAT) and Nacetylserotonin-O-methyltransferase (ASMT) was analyzed by RT-PCR, q-PCR and Western-blot in ram testes, epididymis, and accessory glands. The RT-PCR showed the presence of the m-RNA codifying both AANAT and ASTM in all the tissues under study, but the q-PCR and Western-blot revealed that gene expression of these enzymes was significantly higher in the testis (p < 0.05). Immunohistochemistry confirmed the presence of AANAT and ASMT in the testis and revealed that they were found in the Leydig cells, spermatocytes, and spermatids. Also, measurable levels of melatonin were found in testicular tissue and the tail of the epididymis. In conclusion, our study indicates that the testes are one of the likely sources of the high levels of melatonin found in ram seminal plasma, at least during the day.

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Retinal Localization of the Hydroxyindole-O-methyl Transferase (HIOMT) in the Rat

Cited by 159 publications

References 0 publications

Retinal rhythms in chicks: circadian variation in melantonin and serotonin N-acetyltransferase activity.

Retinal rhythms in chicks: circadian variation in melantonin and serotonin N-acetyltransferase activity.

Control of the Rat Pineal Gland by Light Spectra

Evidence of melatonin synthesis in the ram reproductive tract

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