PubMed Health⌕ Search

Biomedical subjects

J Falcón

Publications and source records attributed to J Falcón.

At least 55 records · Page 3Linked to original sources
PubMed1994

Calciproteins regulate cyclic AMP content and melatonin secretion in trout pineal photoreceptors.

Photoreceptor cells of the fish pineal transduce photoperiodic information into the rhythmic secretion of melatonin. The nocturnal rise in melatonin secretion has been associated with an increase in cyclic AMP (cAMP) production and with an entry of Ca2+ ions through L-type voltage-dependent channels. It is shown here that two inhibitors of calciproteins, W7 and calmidazolium, inhibit melatonin secretion and, to a lesser extent, cAMP levels in cultured trout pineal photoreceptors. Kinetic studies indicated that melatonin secretion was affected earlier than cAMP in cells cultured in the presence of W7. The present results provide evidence that Ca2+ acts through one or more calciproteins to regulate melatonin production. It is suggested that Ca2+/calciprotein complexes might act at two different sites, one involving regulation of cAMP metabolism, and the other being independent from cAMP.

Animals↗
PubMed1994

Immunocytochemical localisation of hydroxyindole-O-methyltransferase in pineal photoreceptor cells of several fish species.

Melatonin is an internal "Zeitgeber," involved in the timing and control of a number of rhythmic functions and behaviours. Its synthesising cells remain to be identified in the fish pineal. The last step in the melatonin biosynthetic pathway is catalysed by the enzyme hydroxyindole-O-methyltransferase. An affinity-purified antibody, directed against chicken pineal hydroxyindole-O-methyltransferase, was used in the present study to identify the melatonin synthesising cells in four fish species: a primitive chondrostean (sturgeon), a saltwater teleost (dorado), and two freshwater teleosts (pike, trout). Western blot immunolabeling of pike and trout pineal proteins revealed a single band at 38 KDa, which corresponds to the known molecular weight of the enzyme in bovine, rat, and chicken pineal. Regardless of the species, a specific immunocytochemical labeling, visualised by means of the peroxidase-antiperoxidase method, was exclusively associated with the photoreceptor cells. These results provide evidence that photoreceptors of the fish pineal are responsible for the biosynthesis of 5-methoxyindoles, including melatonin. In the pike, reactions were less intense in the distal portion of the pineal vesicle than in the other regions of the organ. It is questioned whether this might be related to the existence of a germinative zone, generating new photoreceptor cells in this distal portion. Hydroxyindole-O-methyltransferase has been previously demonstrated in mammalian pinealocytes, and modified photoreceptors of the avian pineal. It is now demonstrated in pineal photoreceptors of a primitive fish and of more evolved saltwater and freshwater fish. The results strengthen the view that these cells are related through phylogeny and that their well conserved melatoninergic function appears early in the course of evolution.

Acetylserotonin O-Methyltransferase↗
PubMed1994

Calcium and melatonin production in dissociated trout pineal photoreceptor cells in culture.

Trout pineal cells maintained in primary culture produce melatonin in high amounts during night time and low amounts during daytime. The dark-induced increase in melatonin production was enhanced, in a dose-dependent manner, by elevating extracellular calcium concentration. Low external calcium concentration reduced nocturnal and diurnal melatonin production. Bay K 8644 increased, in a dose-dependent manner, the dark-induced rise in melatonin output, and this effect was antagonized by nifedipine and verapamil. This suggests a role for the dihydropyridine calcium channels in the regulation of the melatonin output. To confirm this, patch-clamp recordings (whole-cell perforated) were run in a 20 mmol/l barium medium at different holding potentials from -80 mV. A voltage-dependent inward current was activated from -30 mV to +40 mV with a maximal amplitude being observed at 0 mV. This current was drastically increased in the presence of Bay K 8644. Nifedipine inhibited the current both in the absence or in the presence of Bay K 8644. Our results are consistent with the idea that extracellular calcium participates in the control of melatonin secretion by photoreceptor cells. It is suggested that activation of the voltage-dependent L-type channel may modulate this secretion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Multiple circadian oscillators in the photosensitive pike pineal gland: a study using organ and cell culture.

The fish pineal organ contains typical and, in some species, modified photoreceptor cells involved in the photoperiodic control of melatonin production. In the majority of species studied, the rhythm in melatonin production is driven by an intra-pineal circadian oscillator synchronized by the light:dark cycle. In the present study, it is shown that the endogenous rhythm in melatonin release of superfused pike pineals maintained under constant darkness is expressed at temperatures of 19 degrees C, 20 degrees C, 25 degrees C, and 30 degrees C (period > 24 hr), but not at temperatures of 10 degrees C and 15 degrees C. Under constant darkness, pineal fractions containing either typical photoreceptors, modified photoreceptors, or both behaved like total organs. Dissociated pike pineal cells, cultured statically at 20 degrees C, expressed a high amplitude rhythm in melatonin secretion under a light:dark cycle. Under constant darkness, circadian oscillations, which appeared better sustained than in organ culture, were also observed. This study provides the first evidence that the rhythmic production of melatonin, by a fish pineal, is driven by a population of circadian oscillators or clocks. It is hypothesized that each typical and modified photoreceptor might be the locus of a circadian clock. Damping of the overall rhythm under constant darkness might reflect the desynchronization (uncoupling) between these clocks and/or damping of individual oscillators.

Animals↗
PubMed1994

Rhythmic secretion of melatonin by the superfused pike pineal organ: thermo- and photoperiod interaction.

In the pineal organ of the pike (Esox lucius, teleost), the rhythmic production of melatonin by the photoreceptor cells is governed by a population of endogenous circadian oscillators, synchronized and entrained by the light/dark (L/D) cycle. Production of melatonin is inhibited by light and highly increased in the dark. In the present study, isolated and superfused pike pineals were exposed to a 24-hour temperature cycle of high (10 degrees C) or low (4 degrees C) amplitude, either under L/D, or under constant darkness. Under L/D, photoperiod is the dominant entraining stimulus for the melatonin secretion rhythm. It was high during the dark phase and low during the light phase, either under cold light/warm dark or under warm light/cold dark conditions. Under a warm light/cold dark cycle, the amplitude of the melatonin rhythm was reduced. In pineals cultured at 10 degrees C, a 20 degrees C temperature pulse potentiated or reduced the night-induced rise in melatonin production when applied, during the dark or during the preceding light phase, respectively. Under constant darkness, high- or low-amplitude temperature cycles could synchronize the rhythmic production of melatonin, which peaked with the high temperature. However, the shape of the oscillation could appear modified under warm subjective-L/cold subjective-D, depending on the experimental conditions. Finally, the rhythmic release of melatonin synchronized by a temperature cycle under constant darkness was no longer observed after removal of the external zeitgeber. The present study provides direct evidence that the pineal acts as a photothermotransducer.

Animals↗
PubMed1993

Regulation of melatonin production by pineal photoreceptor cells: role of cyclic nucleotides in the trout (Oncorhynchus mykiss).

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.

Animals↗
PubMed1993

[Photoreceptor cells of the pineal body in culture: effect of 17 beta-estradiol on the production of melatonin].

Pineal photoreceptor cells produce the neurohormone, melatonin, a major "Zeitgeber" of the organism. This compound has been involved in the control of development, growth, sexual maturation, and seasonal reproductive cycles. We investigated, here, the effects of estradiol-17 beta on melatonin production by cultured pineal photoreceptor cells. Under a light/dark (LD: 12/12) cycle, cultured trout pineal cells maintained a rhythmic secretion of melatonin with higher amounts being released during the dark phase. The amplitude of the rhythm tended to increase with time spent in culture. Application of estradiol-17 beta during the dark phase of a LD cycle (i.e., for 12 h) affected melatonin release in a dose-dependent manner: low concentrations (10(-10) to 10(-8) mol/l) were inhibitory whereas high concentrations (over 10(-7) mol/l) were stimulatory. When estradiol-17 beta was applied continuously for several 24 h LD cycles, the inhibitory effect observed during the first dark phase disappeared later on. Rather, in the presence of estradiol-17 beta, at the concentrations of 10(-9) and 10(-6) mol/l, a high amplitude rhythm in melatonin secretion was recovered faster, when compared to controls. Replacement of 10% fetal calf serum by 0.1% bovine serum albumin did not affect the responses of the photoreceptor cells to 10(-6) mol/l of estradiol-17 beta. The present results bring the first evidence that estradiol-17 beta modulates melatonin secretion by cultured pineal photoreceptors. They further support the idea according to which sexual hormones exert a feedback regulation on the pineal. Pineal photoreceptors appear as multieffector cells which transduce information from, both, physical (photoperiod) and internal (chemical) factors.

Animals↗
PubMed1992

Long-term effects of constant light or darkness on chicken pineal hydroxyindole-O-methyltransferase expression: biochemical and cellular aspects.

1. Chickens kept in constant light, as opposed to constant darkness, display a twofold increase in the activity of pineal hydroxyindole-O-methyltransferase (HIOMT), the last acting enzyme in the melatonin pathway. 2. Using an immunological approach, we presently show that this regulation of HIOMT activity reflects changes in the concentration of a single molecular form of the enzyme protein (a 38 kDa polypeptide). Immunohistofluorescence indicates that these concentration changes concurrently affect modified photoreceptors and pinealocyte-like cells in the chicken pineal organ. 3. Together, the present data support the hypothesis that environmental lighting might regulate the expression of the HIOMT gene.

Acetylserotonin O-Methyltransferase↗
PubMed1989

Pineal transducers in the course of evolution: molecular organization, rhythmic metabolic activity and role.

Data on the cell biology of pineal transducers (chief cells: typical and modified photoreceptors, pinealocytes) which belong to the paraneuron family, are reviewed in the vertebrate series. In spite of major changes throughout phylogeny, it is proposed that pineal chief cells share a common feature: they somehow transform the information derived from the light/dark cycle into daily rhythms of neural (an excitatory neurotransmitter) and/or hormonal (melatoninergic) output and appear invariably involved in the temporal organization of physiological and behavioral processes.

Animals↗
PubMed1989

Regulation of melatonin secretion in a photoreceptive pineal organ: an in vitro study in the pike.

The pineal organ (or pineal) of a teleost fish, the pike, contains typical (cone-like) and modified photoreceptor cells. Both are involved in indole metabolism, including melatonin production. How photoperiod controls melatonin biosynthesis in organs containing mainly photoreceptor cells, remains unclarified. To tackle this question we have used cultured pike pineal organs to investigate the variations in (1) the activity of the arylalkylamine-N-acetyltransferase (NAT), which is involved in the biosynthesis of melatonin, in static culture and (2) melatonin release in a perifusion system. Serum melatonin was also quantified in pike kept under a 24 hr light/dark (LD) cycle. Under LD conditions, NAT activity, melatonin release, and serum melatonin levels were high during the scotophase and low during the photophase. High-amplitude rhythms in NAT activity and melatonin release were maintained during three 24 hr cycles in constant darkness and a low-amplitude rhythm of NAT persisted in constant illumination. Midnight illumination induced a dramatic decrease of NAT activity and melatonin release. Darkness at midday did not induce a rise of the melatonin release, which occurred only at the onset of the subjective scotophase. From the present data it is strongly suggested that the pineal of the pike contains a circadian oscillator--synchronized by the photoperiod--which generates the rhythms of NAT activity and of melatonin release. Melatonin release, which reflects the rhythmic activity of NAT, might largely contribute to the melatonin circulating levels. The circadian oscillations observed under constant conditions suggest that the oscillator might behave differently in the pike, compared with intrapineal oscillators of 2 other species (lizard and chicken) under investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Melatonin production in organ cultured chicken pineal: modulation by adenosine and its analogs.

The effects of adenosine, of its non-metabolizable analogs, and of compounds related to its metabolism, were investigated in the photosensitive chicken pineal, maintained in static culture or in superfusion. Stimulation or inhibition of melatonin production was obtained, depending on the experimental conditions tested. Endogenous adenosine is involved in the regulation of the melatonin output. The effects of the nucleoside might depend on the balance between its intra- and extracellular pools; (re)uptake mechanisms are most probably involved. It is suggested that cell surface receptors mediate adenosine effects, but intracellular actions (P-site, transmethylation pathways) are not excluded. This investigation is a breakthrough in the field of pineal physiology which offers new perspectives in the study of the control of melatonin production.

2-Chloroadenosine↗
PubMed1987

Rhythmic melatonin biosynthesis in a photoreceptive pineal organ: a study in the pike.

Activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase, involved in the biosynthesis of melatonin from serotonin, were assessed over 24 h in the pineal organ of pikes (Esox lucius, L.; teleosts) entrained to natural (winter) environmental conditions. Only NAT activity exhibited daily changes, rising at the onset of darkness and resuming low values shortly before the end of the scotophase. The rhythm was damped under constant darkness, lower and higher values being shifted towards intermediate ones. NAT activity was lowered under constant light; however, a significant increase was seen at the end of the subjective night, suggesting the existence of a low-amplitude rhythm. Illumination of the pikes at the middle of the scotophase induced inactivation of roughly half of the maximal NAT activity, possibly indicating the existence of one photolabile and one photostable enzymatic component. Under natural conditions, radioassayable melatonin of the pike pineal organ displayed daily variations which paralleled those of NAT activity. Melatonin production thus appears to reflect the daily changes of NAT, synchronized to the light/dark cycle.

Acetylserotonin O-Methyltransferase↗
PubMed1986

Indoles in the photoreceptor cells of the lamprey pineal complex.

In the pineal complex of the brook lamprey, the hydroxyindole-0-methyltransferase (involved in the biosynthesis of 5-methoxyindoles) displays a daily rhythm of activity with a nocturnal peak, during a light/dark cycle and in constant darkness. Immunoreactive indoles were found in both varieties of photoreceptor cells (P1 and P2): serotonin and N-acetylserotonin-like substances in P2 and a melatonin-like compound in P1. It is suggested that P1 and P2 are involved in indole metabolism.

Acetylserotonin O-Methyltransferase↗
PubMed1986

Photoreceptors in the teleost pineal organ. Daily fluctuations of indole metabolism.

The present study in the pineal organ of the pike reports the existence of day/night variations in the levels of three indoles, and in the activity of two enzymes involved in their metabolism. Present and previous data indicate that the cone-like (P) and modified (MP) photoreceptors of the pineal organ translate the photoperiodic information into nervous and indolic (in P), or into indolic (in MP) signals, displaying circadian variations. It is questioned whether these cells which are functional units of the circadian system, contain a circadian oscillator.

Animals↗
PubMed1985

In vitro uptake and metabolism of [3H]indole compounds in the pineal organ of the pike. I. A radiochromatographic study.

Thin layer chromatography analysis of [3H]serotonin and [3H]melatonin metabolites synthetized in vitro by the pineal organ of the pike was performed. After a 10-min pulse, [3H]serotonin was mainly converted into [3H]-5-hydroxyindoleacetic acid (37%), [3H]-5-hydroxytryptophan and [3H]-5-methoxytryptophan (12 to 14%), and [3H]-5-hydroxytryptophol and [3H]-5-methoxytryptophol (3.5 and 9%) at the onset of darkness. When the pulse was followed by postincubations (in a cold medium) of increasing duration (15, 30, and 60 min), it appeared that the amount of [3H]-5-hydroxyindoleacetic acid decreased, that of [3H]-5-hydroxytryptophol decreased faster than that of [3H]-5-methoxytryptophol, and the amounts of [3H]-5-hydroxy- and [3H]-5-methoxytryptophan increased. [3H]-N-acetylserotonin, [3H]melatonin, and [3H]-5-methoxytryptamine were found in very low amounts. At the beginning of the photophase or at the onset of darkness, the uptake and metabolism of [3H]melatonin (after a 10-min pulse followed by a 10-min incubation in cold medium) resulted mainly in the formation of [3H]-5-methoxytryptophol (23 to 43%) and of [3H]-5-methoxytryptamine (6 to 12%). These results show that the pike pineal organ can synthesize all indoles that are known in the pineal gland of higher vertebrates. Usual, but also unusual, pathways of the indole metabolism were found that will need further clarification. Among these are the possible carboxylation of serotonin and deacetylation of melatonin (leading to the synthesis of 5-methoxytryptophol). Altogether, the results obtained suggest that the indole metabolism might be more complex than what has already been described in vertebrates.

Animals↗
PubMed1985

In vitro uptake and metabolism of [3H]indole compounds in the pineal organ of the pike. II. A radioautographic study.

In a previous radiobiochemical study [Falcón et al., 1985] it was demonstrated that the pineal organ of the pike incubated in vitro takes up and metabolizes [3H]serotonin and [3H]melatonin. Parallel to this experiment (present work), pineal organs were investigated by use of light and electron microscopic radioautography to investigate the cell types involved in indole metabolism. Irrespective of the tracer and experimental conditions used, the radioautographic reactions were mainly found in cone-like and modified photoreceptor cells of the pineal parenchyma. Taking into account the limits of the method used as well as previous data concerning the direct photosensitivity of the organ, the localization of exogenous indoles, and the localization and circadian variations of endogenous ones, it is concluded that the photoperiodic information is translated into both nervous and indolic signals in cone-like photoreceptor cells and into indolic signals in modified photoreceptor cells.

Animals↗
PubMed1984

Photosensitivity and biosynthesis of indole compounds in the cells of the receptor line of the pineal organ of the pike.

The pineal organ of the pike is a functional photoreceptive organ in which a multiplicity of the cells of the receptor line (CRL i.e. typical and modified photoreceptors) was demonstrated. The CRL appeared to be (i) regionally distributed, (ii) photosensitive, and (iii) responsible for the storage of various indoles (melatonin and precursors), their levels showing light-dark fluctuations. It is strongly suggested that CRL are photoneuroendocrine transducers in which photoperiodic stimuli are converted into nervous (typical photoreceptors) and neurohumoral (all CRL) messages, displaying circadian variations. CRL appeared to be one of the components by which environmental lighting influences physiological and behavioral processes in fish.

Animals↗