Comparison of the Effects of ?-Adrenergic Agents on Pineal Serotonin N-Acetyltransferase Activity and Melatonin Content in Two Species of Hamsters (original) (raw)
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Journal of Pineal Research, 1985
Thus far, all attempts to stimulate melatonin synthesis by 0-adrenergic receptor agonists in the Syrian hamster pineal gland have failed. Neither a wide range of dosages of isoproterenol (0.5 mg/kg to 24 mg/kg), nor prolonged treatment with norepinephrine, the natural neurotransmitter, increased N-acetyltransferase (NAT) activity or melatonin production. In the present study, the administration of isoproterenol at night was likewise ineffective in advancing or enhancing the normal nightly melatonin peak. Also, we did not find a delayed effect 7 or 8 h after the administration of the drug. Furthermore, we tested the idea of coneurotransmitters such as octopamine or dopamine being possibly necessary for stimulation, but could not find any effect of these substances on melatonin synthesis. In addition, a parasympatholytic agent, atropine, did not increase the responsiveness to sympathomimetic agents. Administration of a phosphodiesterase inhibitor was also ineffective in stimulating NAT activity. On t h e other hand, isoproterenol did retard the drop in NAT and melatonin after lights-on at night, indicating that 0-receptors are involved in maintaining elevated melatonin levels.
A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters
Journal of Pineal Research, 1993
single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters. J. Pineal Res. 1993:14:138-144. Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110-210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to IS0 or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near-basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to IS0 injections at dawn disappeared. In animals exposed to light from 30 min prior to melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA). These results demonstrate that adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and ( 3 ) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase. I injection to the time of sacrifice, I S 0 injections increased pineal
Journal of Pineal Research, 1986
Norepinephrine (NE, 10−6 M) stimulated melatonin accumulation in the incubation medium of rat (but not Syrian hamster) pineals taken at the end of the light phase. However, NE elevated melatonin accumulation in the medium of pineals taken after 20 min of light exposure of animals of either species at 6 h into the 10-h dark phase. A dose response to 10−7−10−5 M NE was observed in both the medium and pineals upon incubation of pineals taken from rats at 4 h into the light phase and from hamsters after 20 min light exposure at 6 h into the dark phase. Approximately 95% of the melatonin present was in the medium. The incubation time was 4 h in all cases. Subcutaneous injection of 1 μg/g NE (either at the end of the light phase or after 30 min of light at 6 h into the dark phase) did not stimulate in vivo Syrian hamster pineal melatonin content determined 1 or 2 h after injection, whether the hamsters were placed in light or darkness after the injection. However, after 30 min of light beginning at 6 h into dark, injection of 5 μg/g desipramine (DMI, a blocker of catecholamine uptake into nerve endings) allowed a dramatic hamster pineal melatonin response to additional injection of 1 μg/g NE, observed at 1 and 2 h in light after injection. A small effect of DMI alone was seen. DMI also potentiated the effect of NE (each 10−6 M) on melatonin accumulation in the medium of incubated hamster pineals taken after a short light exposure at night. No significant stimulatory effect of NE and/ or DMI was seen in vivo or in vitro near the middle of the light phase. Measurement of melatonin in the incubation medium is a useful method for studying pineal function. The Syrian hamster pineal has rhythm of sensitivity to NE (sensitivity evident at night) and even at night is protected by neuronal uptake from circulating NE-induced stimulation of melatonin production. NE appears to be the neurotransmitter for stimulation of pineal melatonin production in the Syrian hamster. The sensitivity rhythm and uptake protection might provide specificity of control of the nightly melatonin signal by reducing the chance of a melatonin response during the day or a response to circulating catecholamines from general sympathetic stimuli.
Journal of Neural Transmission, 1985
Pineal levels of tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and the activities of the enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase were determined in male albino rats and Syrian hamsters that were implanted with the appropriate corticosteroid or adrenalectomized two weeks earlier. Melatonin content and NAT activity were increased at 4 hours (during darkness) in adrenalectomized hamsters; conversely, no alterations in melatonin levels were observed in either adrenalectomized or implanted rats. It is suggested that the changes in adrenal function probably have a minor influence on pineal melatonin production.
Brain Research, 1989
Specific binding of [ 125I]iodo-[β-(4-hydroxyphenyl)-ethylaminomethyl]tetralone ([ 125I]HEAT) was used to assess α1-adrenergic receptors on pineal gland membranes of male Syrian hamsters (Mesocricetus auratus) housed under a 14:10 h light-dark cycle (lights on at 06.00 h). Saturation experiments with pooled pineal membrane preparations showed the presence of α1-adrenergic receptor sites (dissociation constant Kd approx. 0.1 nM). Analysis of 4 time points indicated no significant change in Kd, but significant (P < 0.01) changes of receptor density (Bmax) with a minimum recorded at night. Binding of a constant amount of [ 125I]HEAT (200 pM) to pineal membranes at 8 time points exhibited a circadian variation (P < 0.001) of receptor density with lowest values around midnight and highest levels during daytime.
Life Sciences, 1988
In male rats housed under a 14:10 LD cycle (lights on at 0800h), pineal beta-adrenergic receptors, assessed as 1251odopindolol (IPIN) binding to membrane preparations, showed a 24 hour variation characterized by a nocturnal increase that peaked around middark (2300h-0200h) and a decrease during the latter half of the dark period. Animals exposed to light for 3 hours into the normal dark period showed a similar increase in IP~N binding that was prevented by a single sc injection (0.5 mg/kg) of isoproterenol (ISO). The decrease in IPIN binding observed after middark was prevented both by moving the animals to light at 0200h and by propranolol administration (20 mg/kg). Likewise, the reduction in IPIN binding was induced in light exposed animals both by ISO administration ( in a dose dependent manner) and by injection of norepinephrine (NE) plus the catecholamine uptake blocker desmethylimipramine (DMI). DMI alone was without effect. Chronic denervation of the pineal gland by superior cervical ganglionectomy (SCGx) increased IPIN binding to levels not higher than those observed at middark.
Journal of Pineal Research, 1985
In three separate experiments, the effect of acute exposure to either artificial o r natural light during darkness of pineal N-acetyltransferase (NAT) activity and melatonin content was studied in the cotton rat (Szgmodon hispidus). The exposure of animals to an artificial-light irradiance of 160,000 pW/cm2 during darkness for either 1 s, 5 s, or 30 min was followed by a precipitous decline in pineal NAT activity and melatonin content when measured at either 15 or 30 min after light onset. When cotton rats were acutely exposed to light at night for 5 s, irradiances of either 3.2, 32, 320, and 3,200 did not suppress either pineal NAT or melatonin 30 min later; however, if the 5-s exposure had an irradiance of either 32,000 or 160,000 pWlcm2, the pineal enzyme activity and indole content were depressed. Moonlight, which had a maximal irradiance of 0.32 pW/cm2, was unable to suppress pineal NAT activity and melatonin content even when the animals were exposed to the moonlight for 30 min. The treatment of cotton rats with either norepinephrine or its agonist, isoproterenol, before their exposure to light at night retarded slightly the suppressive effect of light on the pineal constituents measured. Also, these drug treatments suppressed the pre-exposure levels of both NAT activity and melatonin content in the cotton rat pineal gland.
Journal of Pineal Research, 1989
The ontogeny of diurnal rhythm patterns in the pineal and serum levels of melatonin, serotonin, and N-acetylserotonin was studied in Syrian hamsters (Mesocricetus uurutus) from birth to adulthood. The pineal and blood specimens were collected at 1100 h and 0200 h, and the compounds were measured by radioimmunoassay (RIA) procedures. Pineal melatonin and serotonin did not show any circadian rhythm at day 5 of postnatal age. At this age N-acetylserotonin was undetectable in the light phase but became manifest at night. By 10 days of age pineal serotonin registered an established rhythm pattern, with a higher level during the day. The occurrence of circadian rhythm in pineal melatonin was delayed and manifested first at 25 days of age. At this age, the first detectable daytime level of N-acetylserotonin also occurred. Circadian rhythm in serum melatonin was also established at this age. The serum serotonin did not evince any rhythm pattern throughout the observation period, except at day 17 of postnatal age. The massive concentration of daytime serotonin in the pineal was not reflected in the circulatory system. For serum N-acetylserotonin there was no discernable day-night rhythm in all age groups, except at 25 days of age. The results show that the timing of the appearance of various compounds in the neonatal pineal is variable; the release of the substances does not always reflect their synthesis; the ontogenesis of circadian rhythm is a part of the maturational process; and 25 days of age is a rather critical time in development.
Brain Research, 1989
Investigations on the regulation of pineal melatonin synthesis in the Syrian hamster revealed distinct differences compared to this well-understood mechanism in rat. E.g., a circadian profile of pineal norepinephrine (NE) is absent, there is no fl-adrenoceptor sensitivity during daytime and adrenergic receptor supersensitivity is not easily achieved. To elucidate the action of NE on pineal receptor sites, the effects of iontophoretic application of adrenergic compounds on spontaneous electrical discharge rates of pinealocytes were investigated during day-and nighttime. Following application of either NE, isoproterenol or clonidine, cells were activated, inhibited or not affected. Whereas about one-third of the units responded to iontophoretic application of sympathomimetics at daytime, the number of affected cells was doubled during the night. These results demonstrate the involvement of adrenoceptors in the regulation of circadian rhythms in electrophysiological properties of Syrian hamster pinealocytes. Since relatively few cells responded during daytime and inhibitory adrenergic mechanisms dominated at night, the classification of receptors by means of iontophoresis may provide a basis to explain the difficulty to influence pineal melatonin synthesis by sympathomimetics in the Syrian hamster.