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Notes: Abstract: The effects of neuropeptide Y (NPY) on pineal gland cyclic AMP (cAMP) accumulation were investigated using dispersed pinealocytes from rats. NPY inhibited the intracellular cAMP accumulation stimulated by isoproterenol and norepinephrine in a dose-dependent manner during a 10-min incubation of pinealocytes. NPY (1 × 10−7M) also inhibited vasoactive intestinal peptide (VIP)- and cholera toxin–induced cAMP accumulation. The inhibitory effect of NPY on isoproterenol-induced cAMP accumulation was completely abolished by a 5-h pretreatment of pinealocytes with 1 μg/ml of pertussis toxin (PT). These results suggest that NPY participates in modulation of cAMP production in the rat pineal gland through PT-sensitive G protein. Yohimbine, an α2-adrenergic antagonist, blocked NPY inhibition of isoproterenol-stimulated cAMP accumulation. On the other hand, the α2-adrenergic agonist clonidine by itself did not affect cAMP accumulation stimulated by isoproterenol but significantly potentiated NPY action. The present study demonstrates that NPY inhibits β-adrenergic or VIPergic stimulation of the pineal gland cAMP accumulation. The inhibitory effect of NPY is mediated through PT-sensitive G protein. Our results also suggest that NPY exerts its action to affect α2-adrenoceptor function.

Notes: Reiter RJ, Reiter MN, Hattori A, Yaga K, Herbert DC, Barlow-Walden L. The pineal melatonin rhythm and its regulation by light in a subterranean rodent, the valley pocket gopher (Thomomys bottae). J. Pineal Res. 1994; 16: 145–153.〈section xml:id="abs1-1"〉〈title type="main"〉AbstractThe daytime and nighttime levels of pineal N-acetyltransferase (NAT) activity, hydroxyindole-O-methyltransferase (HIOMT) activity, and melatonin were measured in adult male and female valley pocket gophers, Thomomys bottae. This species was chosen for study because it is a subterranean rodent that inhabits burrows whose openings to the surface are closed. Therefore, under field conditions it is estimated that the pocket gopher spends roughly 99% of its time in absolute darkness in underground burrows. When wild captured pocket gophers were maintained under a light dark cycle (light intensity during the day of roughly 140 μ,W/cm2), nighttime levels of pineal NAT activity and melatonin content were higher than values measured during the day; on the other hand, HIOMT activity in the pineal gland was similar in the day and at night. When pocket gophers were exposed to an extended light period (220 μW/cm2) 4 hr into the night, the rise in melatonin synthesis normally associated with darkness onset was not inhibited. Also, when gophers were acutely exposed to a light intensity of 400 μW/cm2 for 1 hr beginning 4 hr after darkness onset, neither high nocturnal levels of pineal NAT nor pineal melatonin contents were reduced. Finally, when pocket gophers were exposed to a 600 (μW/cm2 light intensity at either 4 hr or 8 hr into the dark period, pineal melatonin synthesis remained elevated at a level comparable to that measured in dark-exposed controls. The results show that under controlled laboratory conditions the pineal gland of the valley pocket gopher, a species that in its natural habitat spends about 99% of its time in absolute darkness, exhibits higher melatonin synthesis during night than during the day. While the rhythm in pineal melatonin production in the pocket gopher is clearly synchronized by the prevailing light: dark cycle, high nighttime pineal melatonin synthesis is not readily inhibited by light in the intensity range of 220 to 600μW/cm2. In terms of its relative insensitivity to light at night, the pineal gland of the valley pocket gopher resembles that of other diurnally active rodents.

Notes: Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm2) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.

Notes: Abstract: The purpose of this study was to compare the responses of the Syrian hamster and rat pineal glands in organ culture to vasoactive intestinal peptide (VIP). The endpoints in these studies were the activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), as well as pineal and medium melatonin levels. When rat pineal glands were incubated with either VIP (1 μM) or isoproterenol (1 μM), a β-adrenergic agonist, a significant increase in NAT and HIOMT activities and melatonin levels were observed within 3 hr. Conversely, during the day, VIP (1 μM) was ineffective in stimulating these parameters in hamster pineal gland after incubation times of either 2, 4, 6, or 8 hr. In another experiment, hamster pineal glands were collected from animals killed in the late dark period (after 30 min light exposure). In these glands, isoproterenol promoted NAT activity and melatonin production; however, VIP was ineffective in stimulating either NAT or HIOMT activities; likewise, VIP had no stimulatory effect on pineal melatonin levels at night. Finally, when hamster pineal glands at night were incubated with either 0, 10 nM, 100 nM, 10 μM, or 100 μM VIP, no changes in any parameter of melatonin synthesis were measured. The results indicate that the hamster pineal gland, unlike that of the rat, may not respond to VIP with an increased melatonin production.

Notes: Abstract: The purpose of this study was to examine the day/night levels of pineal melatonin and its rate limiting enzyme N-acetyltransferase (NAT) in relationship to the ratio of 11-cis-to all-trans-retinal. Three-week-old chicks were placed in 12:12 light: dark (LD 12:12) cycle for one week, pineals were collected during the light phase at 1500 (i.e., after 10 hr light), during the dark phase at 1900 (i.e., 2 hr after dark), at 2100 (i.e., 4 hr after dark), and at 2300 (i.e., 6 hr after dark) and after light extension to 1900. The results show that light-sensitive 11-cis-retinal in the chick pineal has the same diurnal rhythm as NAT and melatonin; all constituents increased within 2 hr of darkness onset (at 1900) and reached their peak after 4 hr of dark. All values were lowest during the light phase at 1500. Low values for 11-cis-retinal, NAT, and melatonin were also seen in the group of chicks which experienced light extension to 1900. The data indicate that in vivo light plays a major role in triggering rhodopsin-bound 11-cis-retinal production within 2–4 hr after darkness onset; this change likely serves as the signal for the subsequent formation of the hormonal product of the pineal gland, melatonin.

Notes: Abstract: The possible diurnal variation in cardiac [Ca2++ Mg2+]-dependent ATPase (Ca2+ pump) activity and the influence of pinealectomy and melatonin on this enzyme in rat heart have been studied. Lowest levels of cardiac sarcolemma] membrane [Ca2++ Mg2+]-dependent ATPase activity were measured in late afternoon in rats kept under a 14:10 light:dark cycle. Late in the dark phase the enzyme activity began to increase with the rise continuing until 0900, 3 hr after light onset. These time-dependent changes in [Ca2++ Mg2+]-dependent ATPase activity did not occur in either pinealectomized or light-exposed rats suggesting that melatonin, secreted from the pineal gland during the night, induces the change in [Ca2++ Mg2+]-dependent ATPase activity. In vitro studies in which cardiac tissue was incubated in the presence of melatonin over a wide range of doses showed that this indole stimulated the Ca2+ pump. The half-maximal effect of melatonin was observed at a melatonin concentration of 28 ng/ml. These findings suggest that the daily change in [Ca2++ Mg2+]-dependent ATPase activity in the sarcolemma of heart tissue is a result of the circadian rhythm in pineal melatonin production and secretion. These findings may be applicable to normal cardiac physiology.