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F Amenta

Publications and source records attributed to F Amenta.

At least 145 records · Page 8Linked to original sources
PubMed1993

Autoradiographic localization of [3H]nicardipine binding sites in the human renal artery.

In the present study the pharmacological profile and the anatomical distribution of dihydropyridine-type Ca2+ channels were analyzed in sections of the human renal artery by the use of combined radioligand binding and autoradiographic techniques with [3H]nicardipine as a ligand. The binding of [3H]nicardipine to sections of renal artery was time-, temperature- and concentration-dependent belonging, at least in the range of radioligand concentrations used, to a single class of high-affinity binding sites. The dissociation constant (KD) value was 0.3 nM and the maximum density of binding sites (Bmax) was 248 +/- 16 fmol/mg tissue. The pharmacological profile of [3H]nicardipine binding to sections of human renal artery was consistent with the labeling of dihydropyridine-type Ca2+ channels. In fact, dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkilamine, benzothiazepine or non-selective channel modulators were weak or ineffective competitors. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the renal artery, probably within smooth muscle cells. A smaller accumulation of the radioligand occurred in the tunica adventitia, whereas the tunica intima did not show specific binding. These results indicate that light microscope autoradiography techniques associated with radioligand binding may represent a useful tool for analyzing the localization of receptors or targets of drug action within the arterial wall.

Aged↗
PubMed1993

Reduced density of dopamine D2 receptors in the rat tail artery as a function of age.

The present study was designed to investigate the influence of aging on noradrenaline content and the density and pattern of prejunctional dopamine D2 receptors in the tail (ventral caudal) artery of male Sprague-Dawley rats. Tail artery is frequently used as a model for investigating mechanisms of sympathetic vascular control and contains prejunctional dopamine receptor belonging to the D2 subtype. Noradrenaline levels were reduced in rats of 12 months of age in comparison with 3-month-old animals. A further reduction in catecholamine concentration was found in 24-month-old rats. The density of prejunctional D2 receptors, which was measured in frozen sections of the tail artery by using both radioligand binding and autoradiographic techniques, was reduced by about 35% in 12-month rats in comparison with 3-month rats. A decrease by about 55% versus 3-month rats and by about 20% versus 12-month rats was observed in 24-month-old rats. Neither the pharmacological profile nor the anatomical localization of prejunctional D2 receptors was changed in the rat tail artery as a function of age. The parallel decrease in noradrenaline content and in the density of prejunctional dopamine D2 receptor sites in the tail artery of Sprague-Dawley rats of different ages probably accounts for the lack of an age-related change of prejunctional dopamine D2 receptor-linked responses reported in functional studies.

Aging↗
PubMed1993

Pharmacological characterization and autoradiographic localization of dopamine D1 receptors in the human umbilical artery.

Combined in vitro radioreceptor binding and autoradiographic techniques with [3H]SCH 23390 as a ligand were used to analyze the pharmacological profile and anatomical localization of dopamine D1 receptor sites in sections of human umbilical artery. The ligand was bound to sections of the artery in a manner consistent with the labelling of D1 receptors. These receptors, which show a fetal-to-maternal gradient with the highest concentration near the placenta, are located within the smooth muscle layer of the umbilical artery. The above findings suggest that endogenous dopamine may be involved in the control of the tone of the umbilical artery through the interaction with D1 receptors.

Adult↗
PubMed1993

Radioligand binding and autoradiographic analysis of dopamine receptors in the human heart.

The effects of dopamine on the 3',5-'cyclic adenosine monophosphate (cAMP) generating system were analyzed in membrane particles from the human right and left cardiac ventricle. In addition, the pharmacological profile and the anatomical localization of dopamine receptors were assessed on frozen sections of human cardiac atrial or ventricular tissue. Dopamine increased cAMP levels, in a concentration-dependent manner, in membranes of the right and the left ventricle. These effects were abolished by the beta-adrenoceptor antagonist (-)-propranolol, but not by the D1 receptor antagonist SCH 23390 or by the non selective D1/D2 receptor antagonist haloperidol. No specific binding of the D1 receptor antagonist [3H]-SCH 23390 was noticeable within the atrial or ventricular portions of the heart examined using either radioligand binding or autoradiographic techniques. The D2 receptor antagonist [3H]-spiroperidol, in the presence of concentrations of ketanserin sufficient to block possible binding to 5-HT2 sites, was specifically bound to sections of human heart with a dissociation constant value of about 2.6 nmol/l. The highest density of [3H]-spiroperidol binding occurred in the right ventricle followed, in descending order, by the right atrium, the upper part of the left ventricle, the lower part of the left ventricle, the left atrium and the interventricular septum. The binding profile of [3H]-spiroperidol to sections of human heart was consistent with the labeling of dopamine D2 sites. Light microscope autoradiography revealed silver grains throughout the atrial and ventricular walls and these were frequently accumulated in clusters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Nerve growth factor receptor immunoreactivity in the cerebellar cortex of aged rats: effect of choline alfoscerate treatment.

The rat cerebellar cortex represents an interesting animal model for the analysis of age-dependent changes in brain microanatomy and function. Moreover, the cerebellar cortex contains detectable amounts of nerve growth factor (NGF) and express NGF receptors, which are sensitive to aging. Previous studies of our group have shown that treatment with choline alfoscerate (alpha-glyceryl-phosphorylcholine) countered the loss of nerve cells and fibers occurring with age in the cerebellar cortex. The present study was designed to assess whether treatment for 6 months with a daily dose of 100 mg/kg of choline alfoscerate has any effect on the expression of NGF receptor immunoreactivity in male Wistar rats of 24 months of age. Twelve-month-old rats were used as an adult reference group. NGF receptor immunoreactivity which was developed in the 3 layers of the cerebellar cortex in adult rats was decreased in the neuropil of the molecular layer and in the cytoplasm of Purkinje neurons of rats of 24 months. The number of NGF receptor immunoreactive Purkinje neurons was also lower in the oldest age group, whereas the NGF receptor immunoreactivity in the cytoplasm of granule neurons was unchanged. Treatment with choline alfoscerate increased NGF receptor immunoreactivity in the molecular layer and in the cytoplasm of Purkinje neurons as well as the number of immunoreactive Purkinje neurons but was without effect on NGF receptor immunoreactivity in the granule neurons. These results suggest that choline alfoscerate treatment may increase the expression of NGF receptors in the rat cerebellar cortex.

Aging↗
PubMed1993

Structural changes in the endothelium of the femoral artery of spontaneously hypertensive rats: sensitivity to isradipine treatment.

OBJECTIVE: The present study was designed to investigate the influence of hypertension and of long-term treatment with the dihydropyridine calcium antagonist isradipine on the morphology of the femoral artery in spontaneously hypertensive rats (SHR). DESIGN: Systolic blood pressure (SBP), body weight and morphology of the femoral artery were evaluated, and the ultrastructure of the endothelium was analysed by transmission and scanning electron microscopy. METHODS: SHR were divided into three groups, a control group which was left untreated and two isradipine treatment groups, one at 0.01 mg/kg per day and the other at 0.1 mg/kg per day. Two age-matched groups of Wistar-Kyoto (WKY) rats were included in the study; one group was left untreated and was used as a normotensive reference group and the other was treated with isradipine at 0.1 mg/kg per day. The study lasted 12 weeks. RESULTS: SBP did not change in the WKY rats, whether treated with isradipine or not, but was significantly increased in SHR as a function of age. The lower dose of isradipine did not alter SBP in the SHR, but the higher dose brought SBP values into the normal range after the first week of treatment. Light microscopy of sections of the femoral artery did not reveal any structural differences in the five rat groups examined. Both transmission and scanning electron microscopy showed endothelial alterations in the SHR, together with thickening of the internal elastic lamina. Treatment with isradipine significantly improved the morphology of the endothelium in SHR. The higher dose was more effective, but the lower dose partly countered the hypertension-dependent changes in the morphology of the endothelium. No significant modifications to the structure of the endothelium were noticed in isradipine-treated WKY rats compared with untreated WKY rats. CONCLUSIONS: The results show that structural changes occur in the endothelium of the femoral artery of SHR and that isradipine treatment has a protective effect. This protective effect is probably only partly dependent on the antihypertensive properties of the compound.

Animals↗
PubMed1993

Endothelin-1 displaces [3H]nicardipine binding in sections of human renal artery.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, the actions of which are mediated through interaction with specific ET receptors. Functional evidence has shown that the constrictor effect of ET may require extracellular Ca2+. Ca2+ antagonists of the dihydropyridine family attenuate the vasoconstriction caused by ET. However, the basis of the interactions between ET and dihydropyridine agents are not well understood. Our study was designed to assess whether different concentrations of ET-1 or ET-3 have any effect on [3H]nicardipine binding to sections of human renal artery. [3H]Nicardipine was specifically bound to sections of the human renal artery. Binding sites, which were located primarily over smooth muscle of the tunica media, showed the pharmacologic profile typical of a dihydropyridine Ca2+ channel. Increasing concentrations of ET-1, but not of ET-3, competed dose-dependently with [3H]nicardipine binding. A 1-nM concentration of ET-1 lessened specific [3H]nicardipine binding by approximately 80%. These results suggest the occurrence of an interaction in the human renal artery between dihydropyridine Ca2+ channels and ET-1. This interaction probably accounts for the inhibition of the ET-1-mediated vasoconstriction elicited by nicardipine.

Adult↗
PubMed1993

Muscarinic cholinoceptor subtypes in the rat frontoparietal cortex after ipsilateral lesions of the nucleus basalis magnocellularis.

Muscarinic cholinoceptor subtypes (M1 and M2) were studied in membrane particles of the rat frontoparietal cortex 72 h and 1, 2, 3, and 4 weeks after ipsilateral lesioning of the nucleus basalis magnocellularis (NBM). The affinity of the ligand used to characterize muscarinic cholinoceptors, 3H-quinuclidinyl benzilate did not significantly change in lesioned compared with sham-operated rats as well as the density of high affinity (M1) sites. Low affinity muscarinic cholinoceptors (M2 sites) were significantly decreased in NBM-lesioned rats 72 h and 1 week after lesioning. The density of M2 sites did not significantly differ in lesioned rats 2 or 3 weeks after NBM lesioning, but increased, in comparison with sham-operation 4 weeks after NBM lesioning. These findings suggest that frontoparietal M2 muscarinic cholinoceptors, which probably have a presynaptic localization, are sensitive to NBM lesions. Their changes at different times after NBM lesioning suggest the occurrence of loss, compensation and upregulation of cholinergic projections arising to the neocortex from the NBM.

Animals↗
PubMed1993

Dopexamine hydrochloride in the human kidney: localization, receptor binding and effect on 3'-5'-cyclic adenosine monophosphate generation.

Dopexamine hydrochloride is a synthetic dopamine analogue recently developed to improve myocardial and renal performance in patients suffering from low cardiac output states. The present study was designed to assess the pharmacological profile and the anatomical localization of [3H]-dopexamine binding sites within the human nephron. The effects of dopexamine on the 3'-5'-cyclic adenosine monophosphate (cAMP)-generating system in membrane particles of the human kidney were also investigated. It was found that [3H]-dopexamine was specifically bound by sections of the human kidney. The binding was partly inhibited by the DA-1 receptor antagonist SCH 23390, by the beta 2-adrenoceptor antagonist ICI 118,551 and by the DA-2 receptor antagonist domperidone. The 3 antagonists in combination reduced [3H]-dopexamine binding to nonspecific values. Light microscope autoradiography revealed the accumulation of silver grains, corresponding to [3H]-dopexamine binding sites, within the different portions of the human nephron. The incubation of sections of the human kidney with [3H]-dopexamine plus SCH 23390 caused a remarkable reduction in the density of silver grains within the proximal tubule and the macula densa and a moderate decrease in the density of silver grains within the ascending and descending limbs of the loop of Henle as well as within the distal tubule. The incubation of sections of human kidney with [3H]-dopexamine plus ICI 118,551 caused a pronounced reduction in the density of silver grains within the glomerulus, the limbs of the loop of Henle, the distal tubule and the medullary collecting tubules and a moderate decrease in the density of silver grains within the macula densa and the proximal collecting tubule.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

Autoradiographic localization of dopamine D1 receptors in the human kidney.

The pharmacological profile and the anatomical localization of the selective D1-receptor antagonist [3H][R]-(+)-8-chloro-2,3,4,5-tetrahydro-5-phenyl-1H-3-benzazepin-7 -al- hemimaleate ([3H]SCH 23390) were studied in frozen sections of human kidney by using combined in vitro radioreceptor binding and autoradiographic techniques. [3H]SCH 23390 was bound by sections of human kidney in a manner consistent with the labeling of D1 sites, with a Kd value of 3.87 nM and with a Bmax value of 143 fmol/mg protein. Light microscope autoradiography revealed the highest density of [3H]SCH 23390 binding sites within the macula densa and the proximal tubules followed in descending order by the ascending limb of the loop of Henle, the distal tubules and the descending limb of the loop of Henle. No specific binding was noticeable within the glomeruli or within the epithelium of collecting tubules. [3H]SCH 23390 binding sites were also observed within the medial layer of intrarenal artery branches. These findings show that dopamine D1 receptor sites in the human kidney have a localization similar to that described in laboratory mammals with a higher density of tubular than of vascular receptors. The above data account for the vascular, diuretic and natriuretic effects elicited by D1 receptor stimulation in man.

Adult↗
PubMed1992

Localization of 5-hydroxytryptamine-like immunoreactive cells and nerve fibers in the rat female reproductive system.

The presence of 5-hydroxytryptamine (5-HT)-like immunoreactivity (IR) was studied in the rat female reproductive system using polyclonal antibodies directed against 5-HT. Moreover, 5-HT levels in the ovary, oviduct, uterus, and cervix were measured by high-pressure liquid chromatography with electrochemical detection. The highest 5-HT concentrations were found in the oviduct, followed in descending order by the cervix, the ovary, and the uterus. Most 5-HT-like IR was observed in the cytoplasm of mast cells. These cells were found in the connective tissue around the fimbria, in the oviduct, in the uterus, and in the ovary. Mast cells are clustered in the proximity of the parenchymal blood vessels. Moreover, a few 5-HT-like nerve fibers were found distributed mainly perivascularily in the uterine cervix and in the uterine horns as well as in the oviduct. IR nerve fibers were rarely seen within the ovary. The present data provide direct evidence that 5-HT in the female reproductive system not only is associated with mast cells but is located in nerve fibre-like structures as well. The functional significance of this probable 5-HT-ergic innervation of the female reproductive tract discovered in the present study should be clarified in future investigations.

Animals↗
PubMed1992

Muscarinic cholinergic receptors in the human right coronary artery: a receptor binding and autoradiographic study.

We used a combination of radioreceptor binding and autoradiographic techniques to study the pharmacological characteristics and anatomical localization of [3H]-quinuclidinyl benzilate (QNB) binding sites in the human right coronary artery. The ligand was bound to sections of the human right coronary artery in a manner consistent with the labelling of muscarinic receptors. The addition of pirenzepine or of carbachol to the incubation medium to generate displacement curves was indicative of the presence of M1 and M2 receptors in the right coronary artery. Autoradiography showed the localization of M1 sites primarily in the medial layer of the right coronary artery. M2 sites were located primarily in the adventitia. No [3H]-QNB binding sites were observed in the endothelium. A possible role of muscarinic receptors in the pathogenesis of coronary vasospasm is discussed.

Adolescent↗
PubMed1992

Direct demonstration of dopamine D1-like receptor sites in the ciliary body of the rabbit eye by light microscope autoradiography.

The pharmacological characteristics and the anatomical localization of [3H]-SCH 23390 in sections of the ciliary body of the rabbit eye were analyzed using a radioreceptor assay and autoradiographic techniques. [3H]-SCH 23390 was bound to sections of rabbit ciliary body in a manner consistent with the labelling of D1-like receptor sites. The dissociation constant (Kd) was 0.62 nmol/l, while the maximum binding capacity (Bmax) was 117 +/- 9 fmol/mg tissue. Light microscope autoradiography revealed [3H]-SCH 23390 binding sites within the epithelium of the ciliary processes, which is the ocular structure involved in the secretion of aqueous humor. No specific accumulation of silver grains was noticeable within the iridocorneal angle, which is the structure involved in the outflow of aqueous humor. These findings suggest that the rise in intraocular pressure caused by D1 receptor agonists is probably mediated by an increase of aqueous humor formation rather than by an inhibition of the outflow of aqueous humor.

Animals↗
PubMed1992

Oral choline alfoscerate counteracts age-dependent loss of mossy fibres in the rat hippocampus.

Mossy fibres represent a major intrahippocampal associative pathway. They consist of axons of granule cells of the dentate gyrus and show an age-dependent loss as do the granule cells of the dentate gyrus. The present study was designed to assess whether long-term treatment of rats with choline alfoscerate in their drinking water would be effective in countering the loss of mossy fibres and of granule cells occurring with aging. Choline alfoscerate is a precursor in the biosynthesis of brain phospholipids and increases the bioavailability of choline in nervous tissue. Male Sprague-Dawley rats of 18 months of age were divided into two groups. One group received a daily dose of 100 mg/kg choline alfoscerate for 6 months; the other group was used as an untreated control. Twelve-month-old untreated animals were used as a reference group. The area occupied by mossy fibres, as well as their density, was significantly reduced in 24-month-old control rats in comparison with 12-month-old rats. The same is true for the density granule cells of the dentate gyrus which was decreased by about 20% in the oldest animals. In choline alfoscerate-treated rats both the area occupied by mossy fibres and their density were significantly higher than in age-matched controls. Moreover, the number of granule neurons of the hippocampus was higher by about 7% in choline alfoscerate-treated than in control 24-month-old rats. The above data suggest that choline alfoscerate treatment counteracts some anatomical changes of the rat hippocampus occurring in old age.

Administration, Oral↗
PubMed1992

Changes in glutathione content and localization in rat heart as a function of age.

The influence of aging on glutathione levels and distribution in the heart was studied in male Sprague-Dawley rats of 3 (young), 12 (adult) and 24 (old) months of age using biochemical and histofluorescence techniques, respectively. Biochemical assays of reduced glutathione (GSH) in the right and left ventricles and in the septum showed a significant decrease in GSH levels in adult in comparison with young animals. No further changes were noticeable between adult and old rats. GSH histofluorescence revealed a rather homogeneous distribution of the product of histochemical reaction within both right and left atria in 3-month-old rats. In 12-month-old rats a reduction of GSH histofluorescence in comparison with younger animals was noticeable. The loss is more consistent in the epicardial portion of the right atrium and in the endocardial region of the left atrium. In the atria of 24-month-old rats GSH reactivity was homogeneously distributed throughout the atrial wall and was significantly lower than in young or adult rats. In 3-month-old rats GSH histofluorescence was slightly lower in the epicardial than in the endocardial portions of both ventricles. In adult rats a significant decrease of GSH histofluorescence was noticeable in comparison with 3-month-old rats. The loss is particularly pronounced within the endocardial region of the left ventricle. In 24-month-old rats GSH histofluorescence showed no significant differences between adult rats. However, GSH was more homogeneously distributed throughout the ventricular wall than in adult animals. The significance of these data is discussed in relation to the role that GSH plays in protecting the myocytes against free radical damage.

Aging↗
PubMed1992

Dopexamine hydrochloride in the human heart: receptor binding and effects on cAMP generation.

Dopexamine hydrochloride is a synthetic catecholamine proposed for the short-term treatment of heart failure and postoperative low cardiac output. The pharmacological profile and anatomical localization of dopexamine binding were investigated in sections of right and left ventricle using [3H]-dopexamine and ligand techniques associated with light microscope autoradiography. Its effects on the 3-5-cyclic adenosine monophosphate (cAMP) generating system in membrane particles of the human right or left ventricle were also studied. [3H]-Dopexamine was specifically bound to sections of human right or left ventricle. The binding was time-, temperature- and concentration-dependent and was dissociable. The apparent equilibrium constant of dissociation was 3.5 nM. A decreased [3H]-dopexamine binding capacity from the base to the apex and ventricles was noticeable. The pharmacological profile of [3H]-dopexamine binding to sections of right or left ventricle was consistent with the labelling of both beta 2-adrenoceptors and dopamine DA-2 receptors. The most potent displacer of [3H]-dopexamine was the beta 2-adrenoceptor antagonist ICI 118,551 followed by dopamine, noradrenaline and domperidone. The beta 1-adrenoceptor antagonist metoprolol or the dopamine DA-1 receptor antagonist SCH 23390 were ineffective as displacers of [3H]-dopexamine binding. Light microscope autoradiography revealed the localization of [3H]-dopexamine binding sites within the wall of the human right and left ventricle. The density of silver grains was slightly higher in the right than in the left ventricle and showed a uniform transmural distribution across the ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effect of nicardipine treatment upon cardiac hypertrophy in spontaneously hypertensive rats: a morphometric and ultrastructural study.

OBJECTIVE: The present study was designed to investigate the effect of nicardipine administration upon systolic blood pressure (SBP) and cardiac hypertrophy in spontaneously hypertensive rats (SHR). DESIGN: SBP, heart: and left ventricle: body weight ratios, the cross-sectional area of cardiocytes, and the ultrastructure of the left ventricle were evaluated. METHODS: Ten-week old male SHR and age-matched normotensive Wistar-Kyoto rats were studied for 12 weeks. One group of SHR was treated for 12 weeks with a daily oral dose of 1 mg/kg nicardipine and another group with 1 mg/kg hydralazine; Wistar-Kyoto rats were used as a normotensive control group. Light and electron microscope techniques associated with image analysis and morphometry were used. RESULTS: Nicardipine administration normalized SBP values and significantly reduced the heart: and left ventricle: body weight ratios. Moreover, administration reduced the cross-sectional area of cardiocytes by approximately 38% in subendocardium and by 24% in subepicardium. Hydralazine administration significantly reduced SBP values but had no effect upon heart: or left ventricle: body weight ratios or the cross-sectional area of cardiocytes. Electron microscopy showed that nicardipine treatment was able to reduce the hypertension-dependent changes in cardiac ultrastructure consisting of alternations to intercalated discs and line Z morphology as well as in the decrease of the mitochondria: myofibrils ratio. CONCLUSIONS: The above data indicate that nicardipine administration is able to reduce SBP and to counter the development of structural and ultrastructural changes in cardiac morphology which represent a common complication of arterial hypertension.

Animals↗