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ABSTRACT: The dopamine transporter (DAT) is a protein regulating dopamine concentration in the synaptic cleft through the re-uptake mechanism. The DAT is the main target of psychostimulants and seems to play a pivotal role in neuronal degeneration and different neuropsychiatric disorders involving the dopamine system. Exhaustive research, however, regarding the presence of this protein in human platelets is still inconclusive, although it is thought that it might provide a peripheral tool to serve as a mean of exploring the same structure present in the brain. Therefore, we assessed some binding assays in platelets derived from healthy human subjects by means of 3H-WIN 35,428, a compound which is considered a selective ligand for the labelling of this protein, and by means of 125I-RTI-121, another compound with high specificity for DAT. The results showed that the binding of 3H-WIN-35,428 was too low to enable the detection of any structure; the binding of 125I-RTI-121, on the other hand, revealed the presence of two binding sites with pharmacological profiles similar to that of the serotonin transporter (SERT). In conclusions, therefore, platelets would not seem to be a useful model for exploring the DAT, given the prevalence therein of the SERT and the difficulty of labelling the DAT with the currently available ligands.
Neurochemical Research 04/2012; 31(3):361-365. · 2.24 Impact Factor
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Donatella Marazziti,
Irene Masala,
Stefano Baroni,
Margherita Polini,
Gabriele Massimetti,
Gino Giannaccini,
Laura Betti, Paola Italiani,
Laura Fabbrini,
Carolina Caglieresi,
Cecilia Moschini,
Domenico Canale,
Antonio Lucacchini,
Mauro Mauri
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ABSTRACT: The presence of functional pheromones in axillary extracts in humans is still matter of debate. Scattered data suggest that unidentified human axillary compounds with pheromonal activity may influence mood and this may occur, perhaps, through the modulation of the serotonin (5-HT) system that has been linked to mood by several findings. Therefore, the aim of this study was to assess the possible changes of a peripheral marker of the 5-HT system, i.e., the platelet 5HT transporter, and of some psychological tests, in a group of women who were exposed to male axillary extracts (group 1). A matched group of women who underwent an exposure to a neutral solution, were used as control subjects (group 2). The 5-HT transporter was evaluated by means of the specific binding of (3)H-paroxetine ((3)H-Par) to platelet membranes, as well as by means of (3)H-5-HT reuptake in whole platelets, at baseline (T0) and 1h after the stimulation (T1). The following tests were used: the "Experiences in Close Relationships" questionnaire (ECR), the latest version of the Barratt Impulsiveness Scale (BIS-11) and the Structured Clinical Interview for Mood Spectrum, self-reported version. The dissociation constant (Kd) of (3)H-Par binding showed a significant decrease at T1 only in the women exposed to male axillary extracts, as compared with baseline values, while the Bmax and (3)H-5-HT reuptake parameters did not show any change in both groups. The correlation analyses showed that at T0, the Kd values correlated significantly and positively with the factor of motor impulsiveness in all subjects. Two factors of the BIS-11, in particular, the attentional and the motor impulsiveness were significantly lower at T1 in the group 1. Further, at T1 and still in the group 1, a significant and positive correlation was measured between the Kd values and two ECR attachment styles, the secure and preoccupied, as well as with the ECR anxiety scale. Taken together, these findings suggest that the application of male axillary extracts to women may modify the affinity of their platelet 5-HT transporter, as well as of some impulsiveness and romantic attachment characteristics. The substances responsible for this effect remain to be identified.
Physiology & Behavior 03/2010; 100(4):364-8. · 2.87 Impact Factor
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ABSTRACT: Autoradiographic and binding techniques were used to study the presence of [(3)H]muscimol receptors sites in the carp brain. The radioligand was distributed with an high degree of anatomical selectivity. We found abundant labelling in the cerebellum, in the nucleus diffusus lobi inferioris, and in the torus longitudinalis. No labelling was detected within the epithalamus, thalamus and hypothalamus, while the telencephalon and the rhombencephalon displayed a low density of [(3)H]muscimol receptors sites. Binding assay showed the highest concentration of receptor sites in the nucleus diffusus lobi inferioris and the lowest in the medulla oblongata. Presence of [(3)H]muscimol binding sites within the visceral sensory area was noted. The rank order of displacement efficacy of unlabelled ligands observed, suggested that in brain membranes of carp the receptor binding of [(3)H]muscimol has the same pharmacological specificity previously reported in a large number of experiments with tissue homogenates. A general agreement in binding and autoradiography was observed. The present findings suggested that muscimol receptor could be involved in neuronal pathway controlling basic central actions like gustatory signal processing or spatial learning acquisition and retention.
Comparative Biochemistry and Physiology - Part A Molecular & Integrative Physiology 11/2007; 148(2):324-31. · 2.23 Impact Factor
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ABSTRACT: The dopamine transporter (DAT) is a protein regulating dopamine concentration in the synaptic cleft through the re-uptake mechanism. The DAT is the main target of psychostimulants and seems to play a pivotal role in neuronal degeneration and different neuropsychiatric disorders involving the dopamine system. Exhaustive research, however, regarding the presence of this protein in human platelets is still inconclusive, although it is thought that it might provide a peripheral tool to serve as a mean of exploring the same structure present in the brain. Therefore, we assessed some binding assays in platelets derived from healthy human subjects by means of 3H-WIN 35,428, a compound which is considered a selective ligand for the labelling of this protein, and by means of 125I-RTI-121, another compound with high specificity for DAT. The results showed that the binding of 3H-WIN-35,428 was too low to enable the detection of any structure; the binding of 125I-RTI-121, on the other hand, revealed the presence of two binding sites with pharmacological profiles similar to that of the serotonin transporter (SERT). In conclusions, therefore, platelets would not seem to be a useful model for exploring the DAT, given the prevalence therein of the SERT and the difficulty of labelling the DAT with the currently available ligands.
Neurochemical Research 04/2006; 31(3):361-5. · 2.24 Impact Factor
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ABSTRACT: This study demonstrates, for the first time, by both autoradiography and binding assay that [3H]Ro 15-1788 binds to carp brain with a high degree of anatomical selectivity. Saturation binding of the radioligand was determined in seven anatomically defined regions and suggested the presence of one class of binding sites (Type I-lke). In general, there was a good correlation between the autoradiographic and the binding data. By far, the optic tectum and the vagal, facial, and glossopharyngeal lobes showed the majority of [3H]Ro 15-1788 binding sites. Low to negative concentration of binding sites was detected in the cerebellum. The location of [3H]Ro 15-1788 binding sites in particular brain regions, indicates that benzodiazepine receptors could be associated with pathways involved in the control of basic central functions as spatial learning acquisition and retention, and feeding behaviour.
Journal of Chemical Neuroanatomy 03/2006; 31(2):139-45. · 2.43 Impact Factor
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Donatella Marazziti,
Bernardo Dell'Osso,
Stefano Baroni,
Francesco Mungai,
Mario Catena,
Paola Rucci,
Francesco Albanese,
Gino Giannaccini,
Laura Betti,
Laura Fabbrini, Paola Italiani,
Alessandro Del Debbio,
Antonio Lucacchini,
Liliana Dell'Osso
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ABSTRACT: The formation of social bonding is fundamental for several animals, including humans, for its relevant and obvious impact upon reproduction and, thus, survival of the species. Recent data would suggest that oxytocin might be one of the mediators of this process. Given the paucity of data on the possible involvement of oxytocin in human attachment, the present study was aimed to explore the possible relationships between the plasma levels of this neuropeptide and romantic attachment in healthy subjects. Forty-five healthy subjects who volunteered for the study, were included in the study. The romantic attachment was assessed using the Italian version of the so-called "Experiences in Close Relationships" (ECR), a self-report questionnaire for measuring this parameter in adults. The results showed that attachment anxiety and oxytocin are positively linked in romantic attachment to a statistically significant degree (r = 0.30, p = 0.04), that is, the higher the oxytocin levels the higher the score on the anxiety scale of the ECR. The authors suggest the hypothesis that this link represents one of the biological processes resulting in those rewarding emotions related to romantic attachment.
Clinical Practice and Epidemiology in Mental Health 02/2006; 2:28.
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Laura Bazzichi,
Gino Giannaccini,
Laura Betti,
Giovanni Mascia,
Laura Fabbrini, Paola Italiani,
Francesca De Feo,
Tiziana Giuliano,
Camillo Giacomelli,
Alessandra Rossi,
Antonio Lucacchini,
Stefano Bombardieri
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ABSTRACT: The aim of the study was to evaluate the kinetic parameters of a specific serotonin transporter (SERT) and serotonin uptake in a mentally healthy subset of patients with fibromyalgia. Platelets were obtained from 40 patients and 38 healthy controls. SERT expression and functionality were evaluated through the measurement of [3H]paroxetine binding and the [3H]serotonin uptake itself. The values of maximal membrane binding capacity (Bmax) were statistically lower in the patients than in the healthy volunteers, whereas the dissociation constant (Kd) did not show any statistically significant variations. Moreover, a decrease in the maximal uptake rate of SERT (Vmax) was demonstrated in the platelets of patients, whereas the Michaelis constant (Km) did not show any statistically significant variations. Symptom severity score (tiredness, tender points index and Fibromyalgia Impact Questionnaire) were negatively correlated with Bmax and with Vmax, and positively correlated with Km. A change in SERT seems to occur in fibromyalgic patients, and it seems to be related to the severity of fibromyalgic symptoms.
Arthritis research & therapy 02/2006; 8(4):R99. · 4.27 Impact Factor
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ABSTRACT: In cardiac myocytes, growth responses depend on activation of G protein-coupled receptors interacting with Gq/11 protein subfamily members. Endothelin receptors of the ETA subtype belong to this receptor group inducing hypertrophic responses. To understand the role of ETA receptors and signal transduction proteins in modulating cell growth, we analyzed the pharmacological profile of this receptor, its level of expression together with those of Galpha subunits and the RGS2 protein in cardiomyoblasts differentiating into the cardiac phenotype. H9c2 rat cardiomyoblasts were grown in the presence of 10% fetal bovine serum (FBS) or 1% FBS plus all-trans-retinoic acid to induce the cardiac phenotype. The pharmacological properties of ETA receptors were investigated by competition-binding experiments, whereas the protein expression profile was analyzed by immunoblot and immunocytochemistry. The pharmacological profile of ETA receptors changed during differentiation of cardiomyoblasts into cardiomyocytes, and the amount of expressed receptor appeared to increase. Immunocytochemistry also showed a marked increase of receptor expression on cell membranes of differentiated cardiomyocytes. Among the other signaling proteins examined, both Galphaq/11 and RGS2 expression decreased in cells with the cardiac phenotype. Our results demonstrate that the expression of key proteins (ETA receptor, Galphaq/11, and RGS2) involved in signal transduction of hypertrophic stimuli is modulated during cell differentiation and correlates with the cardiac phenotype.
Journal of Receptor and Signal Transduction Research 02/2004; 24(4):297-317. · 1.59 Impact Factor
