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Biomedical subjects

F Amenta

Publications and source records attributed to F Amenta.

At least 109 records · Page 6Linked to original sources

Dopamine D5 receptor expression is unchanged in peripheral blood lymphocytes in essential hypertension.

The present study was designed to investigate possible changes in the expression of lymphocyte dopamine receptor in essential hypertension. The expression of dopamine D5 receptor was evaluated by radioligand binding techniques using [3H]-SCH 23390 as ligand. Plasma catecholamines, aldosterone levels and plasma renin activity were also measured. Eleven borderline hypertensive patients, 15 patient with the mild essential hypertension, 7 patients with moderate essential hypertension and 5 patients with severe essential hypertension were examined. Plasma catecholamine levels were assayed by high pressure liquid chromatography with electrochemical detection. Dopamine D5 receptor was measured by radioligand binding techniques. Plasma aldosterone levels and renin activity were determined by radio immunoassay. [3H]-SCH 23390 was specifically bound to human peripheral blood lymphocytes. The binding was time-, temperature- and concentration-dependent with a dissociation constant (Kd) value of 0.59 nM and a maximum density of binding sites (Bmax) of 223 pmol/10(6) cells. Dopamine competed with [3H]-SCH 23390 binding in the submicromolar range suggesting the labelling of a dopamine D5 receptor. No changes in the density of [3H]-SCH 23390 binding sites were observed in human peripheral blood lymphocytes between essential hypertensive patients and normotensive subjects. Also catecholamines, plasma renin activity and aldosterone levels were unchanged. In spite of the availability of a sensitive technique for measuring dopamine receptors in human peripheral lymphocytes, no change in their expression was noticeable in essential hypertension. This suggests that dopamine receptor analysis in essential hypertension is not a useful marker for investigating hypertension-dependent changes of the peripheral dopaminergic system.

Adult↗

Autoradiographic localization of dopamine D2-like receptors in the rat adrenal gland.

The pharmacological profile and the anatomical localization of dopamine D2-like receptors were studied in sections of the rat adrenal gland using combined radioligand binding and autoradiographic techniques with [3H]-spiroperidol as a ligand. [3H]-Spiroperidol was bound to sections of the rat adrenal gland in a manner consistent with the labelling of dopamine D2-like receptor sites. The binding was time-, temperature- and concentration-dependent and of high affinity with a dissociation constant (Kd) value of 1.6 +/- 0.04 nM and a maximum density of binding sites (Bmax) of 60 +/- 3.6 fmol/mg tissue. Experiments on the pharmacological specificity of [3H]-spiroperidol binding to sections of the rat adrenal gland suggest the labelling of dopamine D3 and/or D4 receptors. The presence of dopamine D3 and D4 receptors in the rat adrenal gland was confirmed by the demonstration of a specific binding for the D3 radioligand [3H]-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (DPAT) and for the D4 radioligand [3H]-clozapine. Light microscope autoradiography showed the highest accumulation of silver grains which correspond to [3H]-spiroperidol binding sites in the rat adrenal medulla. In the adrenal cortex, where density of silver grains is about 40% lower than in the medulla, the radioligand is accumulated primarily in the zona glomerulosa and to a lesser extent in the zona reticularis. These findings suggest that dopamine D2-like receptor sites in the rat adrenal gland cortex are primarily involved in the modulation of catecholamine secretion from the medulla and of aldosterone secretion from the cortex. The possible relevance of the occurrence of dopamine D3 and D4 receptor subtypes in the adrenal gland is discussed.

Adrenal Glands↗

Age-related changes in the density of muscarinic cholinergic M1 and M2 receptor subtypes in pyramidal neurons of the rat hippocampus.

Age-dependent changes in the expression of muscarinic M1 and M2 cholinergic receptors were assessed in the CA1 and CA3 fields of hippocampus using radioligand binding and autoradiographic techniques with [3H]-pirenzepine and [3H]-AF-DX 116 as ligands. Male Wistar rats of 2 months (young), 12 months (adult) and 27 months (old) of age were examined. Radioligand binding analysis revealed a significant decrease of the density of muscarinic M1 cholinergic receptors with increasing age and no change in muscarinic M2 cholinergic receptors. Autoradiographic evaluation of the number of silver grains developed within the cell body of pyramidal neurons of the CA1 and CA3 fields revealed a decrease of muscarinic M1 cholinergic receptors in the 27-month-old rats in comparison with younger cohorts and no changes in muscarinic M2 cholinergic receptors. These findings suggest that the reduction of muscarinic M1 sites noticed between rats of 2- and 12-months of age using radioligand binding techniques is probably dependent on the loss of hippocampal neurons rather than on the reduction of receptor density per neuron. Our data also indicate that appropriate morphological techniques associated with quantitative analysis may be useful in assessing age-dependent changes in the expression of neurotransmitter receptors by specific neuronal populations. The possible pharmaco-therapeutic relevance of the decreased expression of muscarinic M1 cholinergic receptors by pyramidal neurons of the hippocampus of old rats is discussed.

Aging↗

Nucleus basalis magnocellularis lesions decrease histochemically reactive zinc stores in the rat brain: effect of choline alphoscerate treatment.

The effects of monolateral lesioning of the nucleus basalis magnocellularis (NBM) and of choline alphoscerate treatment on histochemically reactive vesicular zinc stores were assessed in the rat brain using the sulphide-silver histochemical technique. Histochemically reactive zinc stores are located primarily within association fibres of the neuropil of the cerebral cortex as well as in the mossy fibres of the hippocampus. The density of cortical and hippocampal sulphide-silver positive fibres, which might have a role in cognitive and mnemonic processes, parallels the density of zinc-containing presynaptic buttons. Unilateral lesions of NBM caused a remarkable decrease of sulphide-silver positive fibres from the 4th week after lesioning in the neuropil of the ipsilateral fronto-parietal cortex and from the 3rd week in the mossy fibres of the ipsilateral hippocampus. Treatment with choline alphoscerate, which is a precursor in the biosynthesis of brain phospholipids that increases the bioavailability of acetylcholine in the nervous tissue, restored, in part, the density and pattern of sulphide-silver positive fibres in the fronto-parietal cortex and in the hippocampus. The data suggest that, analogously to reports from Alzheimer's disease patients, lesions of the NBM cause a decrease of zinc stores in the rat brain. Choline alphoscerate treatment is able to counter the expression of this phenomenon which accompanies experimental lesions of the NBM.

Animals↗

Muscarinic cholinergic receptors in the hippocampus of aged rats: influence of choline alphoscerate treatment.

The present study was designed to investigate age-dependent changes of muscarcinic M1 and M2 cholinergic receptors in the rat hippocampus using radioreceptor assay and autoradiographic techniques with [3H]pirenzepine and [3H]AF-DX 116 as ligands. The analysis was performed on 2-, 12- and 27-month-old male Wistar rats, considered young, adult and old, respectively. Moreover, the influence of a 6-month treatment with choline alphoscerate on the density and pattern of M1 and M2 cholinergic receptors was assessed. Choline alphoscerate (L-alpha-glyceryl phosphorylcholine) is a precursor in the biosynthesis of several brain phospholipids which increases the availability of acetylcholine in various tissues. Muscarinic M1 cholinergic receptors were significantly decreased with increasing age whereas M2 cholinergic receptors did not show changes. Choline alphoscerate treatment countered, in part, the loss of muscarinic M1 receptor sites in old rats. Light microscope autoradiography revealed a loss of silver grains developed after exposure of sections of hippocampus to [3H]pirenzepine in the stratum oriens of CA1 and CA3 fields in rats of 12 and 27 months in comparison with young animals. Choline alphoscerate restored, in part, the decrease of silver grains noted in old rats. Quantitative analysis of the density of silver grains developed in the cell body of pyramidal neurons of CA1 and CA3 fields processed for the demonstration of muscarinic M1 receptor sites revealed a decrease of these grains in rats of 27 months in comparison with younger cohorts. These findings suggest that the reduction in muscarinic M1 sites noticeable between 2- and 12-month rats is probably dependent on the loss of nerve cells and/or terminals in these hippocampal fields rather than to a reduction of their density per neuron. Treatment with choline alphoscerate increased the expression of muscarinic M1 cholinergic receptors within the cell body of pyramidal neurons of CA1 and CA3 fields compared to age-matched control old rats. Consistent with radioreceptor assay data, no changes in the density of muscarinic M2 cholinergic receptors in the animal groups examined were demonstrated by light microscope autoradiography. The possible pharmacological relevance of the increased expression of muscarinic M1 cholinergic receptors elicited by choline alphoscerate in the hippocampus of aged rats is discussed.

Aging↗

Calbindin D-28k immunoreactivity in the rat cerebellar cortex: age-related changes.

The present study was designed to analyze age-dependent changes in the expression of calbindin D-28k immunoreactivity in the cerebellar cortex of male Wistar rats aged 3 months (young), 12 months (adult) and 24 months (old). Calbindin D-28k immunoreactivity was localized primarily in the cytoplasm of Purkinje neurons and in the basal portion of their dendritic processes entering in the molecular layer. The expression of calbindin D-28k immunoreactivity was highest in Purkinje neurons of adult rats and lowest in Purkinje neurons of old rats. Moreover, the number of Purkinje neurons displaying calbindin D-28k immunoreactivity was decreased in aged rats. These results demonstrate the occurrence of age-related-changes in the expression of immunoreactivity of the Ca2+ binding protein calbindin D-28k in the rat cerebellar cortex. The possibility that impairment in the expression of Ca2+ binding proteins may be involved in changes of intracellular Ca2+ homeostasis reported in aging and in some neuro-degenerative disorders is discussed.

Aging↗

Localisation of dopamine D2-like receptors in pulmonary artery of the human and rabbit but not of the rat.

The present study was designed to investigate the presence of dopamine D2-like receptor sites in the main trunk of the human, rabbit and rat pulmonary artery using combined radioligand binding and light microscope autoradiography techniques. [3H]Spiroperidol was used as a ligand. The presence and the localisation of the sympathetic neuroeffector plexus were also studied using catecholamine histofluorescence techniques. Radioligand binding experiments demonstrated the labelling of a population of dopamine D2-like receptors in sections of human and rabbit pulmonary arteries by [3H]spiroperidol. No specific binding occurred in sections of the rat pulmonary artery. Light microscope autoradiography showed the development of specific silver grains within the tunica adventitia, including the adventitia-media border, of the human and rabbit pulmonary arteries. No specific silver grains were found in sections of the rat pulmonary artery. Studies on the pharmacological characterisation of [3H]spiroperidol binding sites in the human and rabbit pulmonary arteries showed that they are sensitive primarily to domperidone, haloperidol, (-)-sulpiride or bromocriptine, and to a lesser extent to n-propylnorapomorphine, quinpirole or clozapine displacement. This suggests that [3H]spiroperidol binding sites in the pulmonary artery probably belong to the dopamine D2 receptor subtype. Catecholamine histofluorescence techniques revealed a rich plexus of fluorescent adventitial and adventitial-medial nerve fibres in the human and to a lesser extent in the rabbit pulmonary artery. Comparison of the localisation of dopamine D2-like receptor sites and of the sympathetic neuroeffector plexus in the pulmonary artery, suggests a possible prejunctional localisation of these sites.

Aged↗

Neuroanatomy of aging brain. Influence of treatment with L-deprenyl.

The present study was designed to assess the influence of long term L-deprenyl treatment on some microanatomical parameters of aging rat frontal cortex and hippocampus. Male Sprague-Dawley rats of 19 months of age were divided into three groups. Rats of the first group received an oral daily dose of 1.25 mg/kg L-deprenyl; animals of the second group were treated with an oral daily dose of 5 mg/kg L-deprenyl, whereas rats of the third group were left untreated and used as control. Treatment lasted for 5 months, and rats were sacrificed at 24 months. At this age they were considered to be old. Another group of 11-month-old rats was used as an adult reference group. The density of nerve cell profiles and of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes was decreased and increased respectively in the frontal cortex and in the different portions of the hippocampus in old in comparison with adult rats. A decrease in the intensity of sulfide silver staining in the mossy fibers of the hippocampus was also observed in old rats. Moreover, a cytoplasmatic accumulation of lipofuscin was noticeable in old rats as well as a significant increase of the monoamine-oxidase (MAO) B reactivity both in the frontal cortex and in the hippocampus. A higher density of nerve cell profiles, of sulfide silver staining, and fewer astrocyte profiles were noticeable in the frontal cortex and in the hippocampus of old rats treated with 5 mg/kg/day of L-deprenyl. This dose of the compound also significantly reduced lipofuscin accumulation and MAO-B reactivity in old rats. However, the lower dose of the compound did not cause any statistically significant effect on the microanatomical parameters investigated with the exception of sulfide silver staining and lipofuscin accumulation, which were increased and decreased respectively after 1.25 mg/kg per day of L-deprenyl. The above results suggest that long-term treatment with L-deprenyl is able to counter some microanatomical changes typical of the aging frontal cortex and hippocampus in the rat. These changes seem to be in part related to the MAO-B inhibitory activity of L-deprenyl.

Aging↗

Autoradiographic localization of dopamine D1-like receptors in the rabbit pulmonary circulation.

The pharmacological characteristics and the anatomical localization of dopamine D1-like receptors were studied in sections of rabbit lung using [3H]SCH 23390 as a ligand. [3H]SCH 23390 was bound to sections of rabbit lung in a manner consistent with the labelling of dopamine D1-like receptors. The binding was time-, temperature-, and concentration-dependent belonging to a single class of high affinity sites. The dissociation constant value (Kd) was 2.05 nM, whereas the maximum density of binding sites (Bmax) averaged 85 +/- 4 fmol/mg tissue. The pharmacological profile of [3H]SCH 23390 binding to sections of rabbit lung is consistent with the labelling of dopamine D1 receptors. Light microscope autoradiography revealed the development of silver grains which correspond to [3H]SCH 23390 binding sites within the tunica intima and the tunica media of large intrapulmonary artery branches. The presence of silver grains was also observed in the tunica media, but not in the tunica intima of medium-sized pulmonary artery branches. No silver grains were observed in small-sized pulmonary artery branches or in the pulmonary veins. Dopamine D1-like receptors localized in the rabbit pulmonary circulation probably mediate vasodilatation. Further work is necessary to clarify the functional significance of the non-homogeneous distribution of dopamine D1-like receptor sites in the pulmonary circulation.

Animals↗

Age-dependent changes in gp75LNGFR (low-affinity nerve growth factor receptor) immunoreactivity in the rat cerebellar cortex.

The expression of gp75LNGFR (low-affinity receptor of the nerve growth factor (NGF) family of neurotrophins) immunoreactivity was studied in the cerebellar cortex of male Wistar rats of 3 months (young), 12 months (adult) and 24 months of age using immunohistochemical techniques and a monoclonal antibody against rat-gp75LNGFR. The percentage of Purkinje neurons displaying gp75LNGFR immunoreactivity (IR), and the intensity of gp75LNGFR IR in the cytoplasm of Purkinje and granule neurons, and in the neuropil of molecular layer of the cerebellar cortex were determined by quantitative image analysis and microdensitometry. The number of Purkinje neurons displaying gp75LNGFR IR and the intensity of gp75LNGFRIR in the cytoplasm of Purkinje neurons was significantly higher in rats of 12 months of age in comparison with 24- and 3-month-old rats. No significant changes were observed in the intensity of gp75LNGFRIR in the granule neuron layer of young, adult and old rats. In the molecular layer, the highest gp75LNGFRIR was found in young animals. It was reduced as a function of age. The present results show that changes in gp75LNGFRIR observed as a function of age affect to a different extent the three layers of the rat cerebellar cortex.

Aging↗

Autoradiographic localization of dopamine D2-like receptors in the rabbit pulmonary vascular tree.

In the present study, the pharmacological characteristics and the anatomical localization of dopamine D2-like receptor sites in the extraparenchymal and in the intraparenchymal portion of the rabbit pulmonary artery were investigated using combined radioligand binding and light microscope autoradiography with [3H]-spiroperidol (spiperone) as a ligand. The ligand was bound to sections of the pulmonary artery in a manner consistent with the labelling of dopamine D2-like receptors with an equilibrium dissociation constant (Kd) of about 2.4 +/- 0.07 nmol/l and a maximum density of binding sites of 65 +/- 4.5 fmol/mg tissue. In contrast, binding experiments made with sections of rabbit lung did not allow the evaluation of specific binding. Light microscope autoradiography showed the development of specific silver grains within the tunica adventitia of extraparenchymal branches of rabbit pulmonary artery and of large and, to a lesser extent, of medium-sized intraparenchymal branches of the pulmonary artery. No silver grains were found within small branches of the pulmonary artery or of the pulmonary vein. Development of adventitial silver grains was inhibited by compounds active at dopamine receptors. The greater sensitivity to displacement by domperidone, haloperidol, (-)-sulpiride and bromocriptine than to displacement by N-propyl-norapomorphine, quinpirole or clozapine suggests that the [3H]-spiroperidol binding sites observed in extraparenchymal, large and medium-sized branches of the pulmonary artery belong, probably, to the dopamine D2 receptor subtype. The possible pre-junctional localization of these sites is discussed.

Animals↗

Expression of neurofilament proteins in the rat cerebellar cortex as a function of age: an immunohistochemical study.

The present study was designed to assess changes in the expression of cytoskeletal proteins in the cerebellar cortex of rats of different ages using immunohistochemical techniques associated with image analysis. Male Wistar rats of 3 months (young), 12 months (adult) and 24 months (old) were used. Neuronal cytoskeleton was investigated using monoclonal antibodies to phosphorylated neurofilament (NF) proteins of high (H), medium (M) and low+H+M molecular weight (NF triplet). In young and adult rats in which the expression of phosphorylated NF immunostaining was similar, a dark-brown immunoreactivity was observed primarily in axons of the white matter and of basket neurons which surround Purkinje neurons and enter in the molecular layer. In adult rats a NF-H immunoreactivity was sometimes observed within the dendritic tree of Purkinje neurons. A significant decrease in the density of NF immunoreactivity involving the three different subunits investigated was found in the cerebellar cortex of old rats. This suggests that cytoskeletal abnormalities occur not only in senile dementia, but also in the so called 'physiological aging'. The cerebellar cortex may represent an interesting model for evaluating age-dependent changes of cytoskeleton.

Aging↗

Influence of long-term treatment with L-deprenyl on the age-dependent changes in rat brain microanatomy.

The present study was designed to assess whether treatment with the monoamine oxidase-B (MAO-B) inhibitor L-deprenyl, which has been documented to increase both mean and maximum survival in aged rats as well as sexual performance and cognitive function, has any effect on the age-related microanatomical changes occurring in the rat brain. Male Sprague-Dawley rats received a subcutaneous injection of 0.25 mg/kg L-deprenyl every other day from the 19th to the 24th month of age. Age-matched control rats were injected with saline, whereas 11-month-old untreated rats were used as an adult reference group. Both body and brain weight were increased as a function of age, and they were unaffected by treatment with L-deprenyl. The density of nerve cell profiles in the frontal cortex, in the CA-1 and CA-3 subfields of the hippocampus, in the dentate gyrus and in the cerebellar cortex were decreased in aged rats in comparison with adult rats. The density of nerve cell profiles in the above brain areas of L-deprenyl-treated rats was not significantly higher in comparison with age-matched control animals with the exception of Purkinje neuron profiles. The intensity of Nissl's staining, which may be related to the protein synthetic capabilities of nerve cells, is reduced within pyramidal neurons of the hippocampus and Purkinje neurons of the cerebellar cortex of aged rats. The intensity of Nissl's staining in L-deprenyl-treated rats was not different from adult rats. Lipofuscin deposition was significantly increased within the cytoplasm of pyramidal neurons of the frontal cortex, of the CA-3 subfield of the hippocampus and of Purkinje neurons of the cerebellar cortex. L-Deprenyl administration decreased lipofuscin accumulation within the cytoplasm of the above mentioned nerve cell types. The density of sulphide-silver staining in the intrahippocampal pathway of mossy fibres, which participate in the elaboration of passive avoidance responses, is decreased in aged rats. Treatment with L-deprenyl counters this age-related reduction. The above results suggest that long-term treatment with L-deprenyl is able to counter the expression of some microanatomical changes typical of aging brain.

Aging↗

Influence of treatment with L-deprenyl on the structure of the cerebellar cortex of aged rats.

Treatment with L-deprenyl increases mean and maximum life span in the rat and reverses memory and learning deficits associated with old age. Since only sparse information is available concerning the influence of L-deprenyl administration on the aging brain microanatomy, we have investigated the effect of long-term treatment with L-deprenyl on the structure of the cerebellar cortex in the aged rat. The cerebellar cortex was used since it represents a useful model for assessing age-related changes in nervous system anatomy and function. Male Sprague-Dawley rats were treated from the 19th to the 24th month of age with a daily oral dose of 1.25 mg/kg or 5 mg/kg L-deprenyl. Age-matched rats were left untreated and used as a control group. Eleven-month-old untreated rats were used as an adult reference group. The density of Purkinje and granule neuron profiles as well as the intensity of Nissl's staining within the cytoplasm of Purkinje neurons were reduced in 24-month in comparison with 11-month rats. Moreover, an increased accumulation of lipofuscin was noticeable in the cytoplasm of Purkinje neurons of old rats as well as an increase in MAO-B activity in the molecular layer of the cerebellar cortex. The two doses of L-deprenyl increased the density of both Purkinje and granule neuron profiles and the intensity of Nissl's staining in the cytoplasm of Purkinje neurons and reduced lipofuscin deposition within Purkinje neurons. The lower dose of L-deprenyl caused only a slight decrease in MAO-B activity, whereas the 5-mg/kg/day dose remarkably reduced it. These results suggest that long-term treatment with L-deprenyl counters the expression of some age-related microanatomical changes in the rat cerebellar cortex. The possible independence of the effects of the compound on age-related microanatomical changes of the cerebellar cortex and on MAO-B inhibitory activity is discussed.

Aging↗

Effect of treatment with the dihydropyridine-type calcium antagonist darodipine (PY 108-068) on the expression of neurofilament protein immunoreactivity in the cerebellar cortex of aged rats.

The effect of long-term treatment with the dihydropyridine-type Ca2+ antagonist darodipine (PY 108-068) on the expression of neurofilament (NF) protein (200 kDa-NF subunit) immunoreactivity in the cerebellar cortex of aged male Wistar rats was assessed using immunohistochemical techniques associated with image analysis. In 12-month-old rats (adult) used as reference animals, 200 kDa-NF subunit immunoreactivity was observed primarily in axons of basket neurons localized in the molecular layer and surrounding the cell body of Purkinje neurons. A specific immunoreactivity was also found in the initial segment of Purkinje neuron axons, and in axons of the white matter of the cerebellar cortex. In 24-month-old rats (aged) a significant decrease in the area occupied by immunoreactive structures was noticeable in comparison with adult animals. A 6-month treatment (from the 18th to the 24th month of life) with an oral daily dose of 10 mg/kg of darodipine restored in part the expression of 200 kDa-NF subunit immunoreactivity in the cerebellar cortex. These data indicate that treatment with the dihydropyridine-type Ca2+ channel blocker darodipine is able to counter in part the age-related loss in the expression of NF protein in the rat cerebellar cortex. This suggests that darodipine may reduce neuronal cytoskeletal changes occurring in aging and in neurodegenerative disorders.

Aging↗

Choline acetyltransferase and acetylcholinesterase in the hippocampus of aged rats: sensitivity to choline alphoscerate treatment.

The influence of aging on the acetylcholine synthesising and the degrading enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) was studied in the hippocampus of male Wstar rats at 2 months (young), 12 months (adult) and 27 months (old) of age using biochemical, immunocytochemical and histochemical techniques. The influence of treatment for 6 months with a daily dose of 100 mg/kg of choline alphoscerate (L-alpha-glycerylphosphorylcholine) on the parameters examined was also investigated in old rats. Biochemical analysis of ChAT and AChE revealed the highest of the enzymatic activities in the hippocampus of adult rats and no significant differences between young and old animals. Immunocytochemical analysis of ChAT immunoreactivity revealed the highest immunostaining in adult rats followed in descending order by young then old animals. Histochemical evaluation of AChE reactivity revealed the highest expression in adult rats followed in descending order by old then young animals. Biochemical analysis of the effects of choline alphoscerate did not reveal any effect on ChAT activity and in increased expression of AChE activity. Moreover, the compound restored, in part, ChAT immunoreactivity in the hippocampus of old rats and increased the expression of AChE reactivity primarily in the CA3 sub field in old rats. The above results suggest that appropriate quantitative immunocytochemical and histochemical techniques may represent a useful tool for assessing age-dependent changes in cholinergic neurotransmission markers. The functional and pharmacological significance of the effects of choline alphoscerate on the expression of ChAT and AChE in the hippocampus of aged rats should be clarified in future studies.

Acetylcholinesterase↗

Pharmacological characterization and autoradiographic localization of dopamine D1-like receptors in the thymus.

The present study was designed to identify the pharmacological profile and the anatomical localisation of dopamine D1-like receptor sites in the rat thymus using [3H]SCH 23390 as a ligand. [3H]SCH 23390 was specifically bound to sections of the thymus. Binding was time, temperature and concentration-dependent belonging in the range of concentrations of radioligand used to a single class of high affinity sites. The dissociation constant was 1.6 nM and the maximal density of binding sites averaged to 170 fmol/mg tissue. The pharmacological profile of [3H]SCH 23390 binding to sections of the rat thymus is consistent with the labelling of dopamine D1-like sites. Dopamine was able to compete with [3H]SCH 23390 binding to sections of rat thymus in the range of nanomolar concentrations. This suggests the labelling of dopamine D5 receptor sites. Light microscope autoradiography revealed the localisation of [3H]SCH 23390 binding sites primarily in the cortex of the thymus and in lesser amounts at the level of thymic corpuscles. The possible functional significance of dopamine D1-like receptors in the rat thymus is discussed.

Animals↗

Dopamine D5 receptors in human peripheral blood lymphocytes: a radioligand binding study.

In the present study we have investigated, using radioligand binding techniques and the dopamine receptor antagonist [3H]SCH 23390 as a ligand, the existence of specific dopamine D1-like receptors in human peripheral blood lymphocytes. [3H]SCH 23390 binding to human peripheral blood lymphocytes was time-, temperature-, concentration-dependent and of high affinity with a dissociation constant value (Kd) of 0.58 +/- 0.05 nM and a maximum binding density (Bmax) of 11.02 +/- 0.3 fmol/5 x 10(6) cells. The binding was also reversible. Pharmacological analysis displacement curves of [3H]SCH 23390 binding with dopamine competing with the radioligand in the submicromolar range suggests that peripheral blood lymphocytes express dopamine D5 receptors rather than dopamine D1 receptors. These results, which are consistent with studies performed with molecular biology techniques, suggest that dopamine may modulate peripheral blood lymphocyte activity. Radioligand binding techniques, applied to lymphocyte receptor studies for their feasibility and flexibility may be used to investigate the possible relationship between the immune and dopaminergic systems. Moreover, they could be employed as a tool in Parkinson's disease, migraine, schizophrenia and hypertension research.

Adult↗