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L F Agnati

Publications and source records attributed to L F Agnati.

At least 19 recordsLinked to original sources
PubMed1995

Receptor-receptor interactions and their relevance for receptor diversity. Focus on neuropeptide/dopamine interactions.

Receptor diversity in combination with receptor-receptor subtype specific interactions, which can be antagonistic or synergistic in character, markedly increase plasticity in WT and VT in the nervous system. In this way switching among transmission lines for the various DA receptor subtypes becomes possible. Some of these aspects are supported by our work on selective modulation of D2 receptors by CCK and NT. Selective regulation of D2 receptors via CCK-8 receptor subtypes and NT receptors may underlie CCK/DA interactions and NT/DA interactions in the basal ganglia. These studies underline the importance of receptor-receptor interactions exerted at the membrane level between neuropeptide receptors and D2 receptors, which are determined at least in part by the ongoing activity at D1 receptors. In the case of both CCK/D2 and NT/D2 receptor interactions, it has been possible, by means of intrastriatal and intraaccumbens microdialysis, to obtain a functional correlate to the receptor interactions found in the membrane preparations from the striatum. Schizophrenia may be in part related to reduced release of CCK and/or NT peptides or to alterations in their receptor interactions with the D2 receptor. This view may lead to new therapeutic approaches.

Animals↗
PubMed1995

Long distance pathways of diffusion for dextran along fibre bundles in brain. Relevance for volume transmission.

Texas Red-labelled dextran with a mol. wt of 3000 g mol-1, a marker for the extracellular space, was injected unilaterally into the neostriatum of adult rats (0.3-30 micrograms microliter-1) and its distribution evaluated 1 min to 5 h later. Diffusion in the neuropil was observed with clearance starting after 30 min. After 10-15 min strong labelling along the myelinated fibre bundles was observed in the entire neostriatum. After about 20 min the labelling along the fibres reached into the corpus callosum and the overlaying deep layers of the cerebral cortex. A marked cellular uptake and accumulation of labelled dextran was found in putative perivascular pericytes. Thus, in the living brain preferential extracellular fluid pathways for diffusion exist, especially along fibre bundles, which allow the exchange of chemical signals between two distant regions. These may represent extracellular fluid pathways for volume transmission.

Animals↗
PubMed1995

On the cellular localization and distribution of carbonic anhydrase II immunoreactivity in the rat brain.

Evidence is provided that carbonic anhydrase-II is localized in the central nervous system to wide spread systems of oligodendrocytes and restricted astroglia populations, involving both fiber bundles and neuropil. It is suggested that CO2 formed in activated axons may, via carbonic anhydrase-II, give rise to protons controlling the excitability of surrounding neuropil. Thus, CO2 may represent an important, highly diffusible, signal in brain, involved in the tonic control of neuronal activity.

Animals↗
PubMed1995

Presynaptic A2-adrenoceptors and neuropeptide Y Y2 receptors inhibit [3H]noradrenaline release from rat hypothalamic synaptosomes via different mechanisms.

Presynaptic receptors may reduce transmitter release with different mechanisms. Both the alpha 2-agonist, clonidine and the Y2-agonist, neuropeptide Y fragment 13-36 (NPY 13-36), induce a concentration-dependent inhibition of the 4-aminopyridine (4-AP)-evoked [3H]noradrenaline ([3H]NA) release from hypothalamic synaptosomes. Changes in alpha 2- and Y2-modulation of noradrenaline (NA) release were observed by lowering the calcium influx with the use of omega-conotoxin (omega-CgTx), a calcium-channel blocking agent. In these experimental conditions, clonidine was less active, whereas NPY 13-36 preserved its efficacy. It therefore seems possible that presynaptic alpha 2-adrenoceptors can primarily inhibit NA release by reducing calcium influx via voltage-sensitive calcium channels (VSCC), while Y2-receptors may inhibit the intracellular release process with a mechanism independent of the calcium entry.

4-Aminopyridine↗
PubMed1995

Counteraction of NYP-induced c-Fos expression in the nucleus tractus solitarii by alpha 2 receptor agonists.

Neuronal c-Fos protein-like immunoreactivity (c-Fos IR) in parts of the nucleus tractus solitarii (NTS)-dorsal motor nucleus of the vagus nerve (dmnX) complex of the anaesthetized rat was studied 90 min after NTS microinjections of neuropeptide Y (NPY) and/or adrenergic receptor agonists in relevant cardiovascular doses. Microinjections of NPY and l-adrenaline alone into the NTS induced neuronal c-Fos IR in parts of the NTS-dmnX complex, while clonidine had no action. No double-labelled GFAP/c-Fos immunoreactive cells were found in the NTS-dmnX complex after the microinjection of NPY into the NTS. Coinjections of NPY and l-adrenaline or clonidine into the NTS reduced the NPY-induced increase in c-Fos IR. The results emphasize that during cardiovascular regulation NPY receptors can control neuronal gene expression in the NTS-dmnX complex via c-fos and that stimulation of alpha 2-adrenoceptors can attenuate NPY receptor transduction also in terms of induction of c-Fos IR in the NTS-dmnX complex via an antagonistic alpha 2/NPY receptor interaction.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1995

Effect of endothelin-1 induced ischemia on peroxidative damage and membrane properties in rat striatum synaptosomes.

Synaptosomes obtained from rat striata lesioned by central injection of endothelin-1 (ET-1) were analyzed for the levels of lipid peroxidation products, the susceptibility to lipid peroxidation, the phospholipid and free fatty acid composition and the activity of Na+,K(+)-ATPase one hour after ET-1 treatment. The intrastriatal injection of ET-1 promoted an increase of endogenous thiobarbituric reactive substances (TBARS), as index of free radical mediated lipid damage, and a greater susceptibility to iron/ascorbate-induced lipid peroxidation. The pattern of free fatty acids showed a significant decrease of arachidonic and docosahexaenoic acid consequent to ET-1 treatment. The analysis of lipid composition showed a significant loss of phospholipids: among phospholipid species, sphingomyelin and phosphatidylethanolamine plasmalogen were particularly reduced by ET-1 treatment. The activity of membrane-bound Na+,K(+)-ATPase was also significantly reduced in synaptosomes obtained from ET-1 lesioned striata. Taken together these results indicate a significant modification of synaptosomal membrane of ET-1 treated rat striata, possibly due to a free radical mediated damage.

Animals↗
PubMed1995

Changes in glucocorticoid receptor immunoreactivity after adrenalectomy and corticosterone treatment in the rat testis.

The distribution of glucocorticoid receptor (GR) in the rat testis was investigated by means of immunocytochemistry (IR) and computer-assisted image analysis. A monoclonal antibody against rat liver GR showed the presence of GR IR selectively in the nuclei of interstitial and tubular cells. The semiquantitative microdensitometry of GR IR revealed that 77% of the specific staining was localized in the tubular compartment of rat testis. After adrenalectomy, GR IR was greatly reduced both in interstitial and tubular cells, roughly at the same degree. Corticosterone treatment (50 mg/kg, for 5 d) of adrenalectomized animals yielded a recovery of nuclear immunopositivity without changing the cellular distribution of GR, as observed in control rats. Nevertheless, the high dose of corticosterone administered produced a significant (p < 0.01) decrease of GR IR with respect to control rats. These results provide evidence for a prevalent nuclear binding of GR in the tubular compartment in basal conditions. On the other hand, adrenalectomy or repeated corticosterone treatment seem to affect GR similarly in all positive cells without changing significantly the proportion of GR IR in the different testicular compartments. This uneven distribution of GR IR suggests that tubular cells can be a major target of corticosterone when affecting directly testicular functions in the rat.

Adrenalectomy↗
PubMed1995

A brief appraisal on some aspects of the receptor-receptor interaction.

Receptor-receptor interaction is being recognized as a key cellular mechanism responsible for the integration of signals between different transmission lines at the membrane level. Receptor-receptor interaction extends the classical concept of integration of depolarization and hyperpolarization effects to the integration of chemical events at membrane level. In the present paper only some hypotheses on the possible mechanistic aspects of the interactions between the membrane receptors will be discussed. Furthermore, possible functional consequences of receptor-receptor interaction will be explored. The limitations of the present experimental approaches to the study of receptor-receptor interaction will also be analysed.

Animals↗
PubMed1995

Temporal changes in sulphated glycoprotein-2 (clusterin) and ornithine decarboxylase mRNA levels in the rat testis after ethane-dimethane sulphonate-induced degeneration of Leydig cells.

Short- (3-24 h) and long-term (4-50 days) changes in sulphated glycoprotein-2 (SGP-2) and ornithine decarboxylase (ODC) mRNA levels in the adult rat testis were studied following a single dose of ethane-dimethane sulphonate (EDS), to destroy the Leydig cells. Distribution patterns of SGP-2 and ODC labelling were consistent with prevailing expression of the two transcripts in Sertoli cells and germ cells, respectively. This pattern did not show appreciable changes following EDS administration. No labelling of SGP-2 mRNA was noted in the interstitium of control and EDS-treated rats. This finding indicates that Leydig cell death induced by EDS is not associated with increased SGP-2 mRNA levels, a phenomenon related to apoptotic cell death in many tissues. Semi-quantitative densitometric analysis of the preparations demonstrated differential changes in SGP-2 and ODC mRNA levels in the tubular compartment following EDS treatment. At 6, but not at 3 and 12, h following EDS administration, SGP-2 mRNA levels showed a significant increase, possibly secondary to a direct effect of the alkylating agent on Sertoli cells. A significant decrease in ODC mRNA levels was observed from day 7 to day 28, matching degenerative changes in the seminiferous epithelium. In contrast, a decrease in SGP-2 transcript levels was observed from days 21-35 after treatment. In conclusion, our findings demonstrate that SGP-2 mRNA, a putative marker of apoptosis, is not altered in the testicular interstitium during EDS-induced degeneration of Leydig cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Different classes of volume transmission signals exist in the central nervous system and are affected by metabolic signals, temperature gradients and pressure waves.

Volume transmission (VT) is the mode of intercellular communication involving the diffusion of transmitters, via extracellular fluid (ECF) pathways, from nerve cells selectively capable of producing the signal (signal source) to nerve and glial cells selectively capable of recognizing it (signal target). The proposal is now put forward that at least two classes of VT signals can be distinguished: (a) the private-code signals, exemplified by neurotransmitters, which are released by a limited group of nerve cells and recognized, via high affinity G-protein coupled receptors or by cytosolic enzymes such as guanylate cyclase in the case of nitric oxide, by a specific group of cells; and (b) the accessible-code signals, such as the electrical signals that are released by all neuronal cells and decoded by almost every CNS cell. In the present paper, it will be underlined that carbon dioxide, hydrogen ions, temperature gradients and pressure waves may be regulators of wiring transmission and VT.

Animals↗
PubMed1994

Antagonistic regulation of alpha 2-adrenoceptors by neuropeptide Y receptor subtypes in the nucleus tractus solitarii.

The modulation of alpha 2-adrenoceptors by neuropeptide Y Y1 and neuropeptide Y Y2 receptor subtypes has been studied in the nucleus tractus solitarii of the male rat. The autoradiographical experiments showed that neuropeptide Y-(1-36), neuropeptide Y-(13-36), a selective neuropeptide Y Y2 receptor agonist, and [Leu31,Pro34]neuropeptide Y, a selective neuropeptide Y Y1 receptor agonist, in the nanomolar range increased the Kd value of the [3H]p-aminoclonidine binding sites in the above rank order of potency without changing the Bmax values. In contrast, in the competition experiments, the neuropeptide Y Y1 and the neuropeptide Y Y2 receptor agonists decreased and increased, respectively, with the same potency the IC50 value of l-adrenaline and especially of clonidine for the alpha 2-adrenoceptor agonist binding sites associated with an increase and a decrease of the B0 value, respectively. Cardiovascular experiments showed that microinjections of clonidine into the nucleus tractus solitarii induced dose-dependent vasodepressor and bradycardiac responses. Threshold doses for vasodepressor effects of neuropeptide Y-(1-36) and of the neuropeptide Y Y1 receptor agonist and for vasopressor effects of the neuropeptide Y Y2 receptor agonist significantly counteracted the vasodepressor action elicited by an ED50 dose of clonidine in the nucleus tractus solitarii, the bradycardiac action of clonidine also being counteracted by the neuropeptide Y Y2 but not the neuropeptide Y Y1 receptor agonist. The present results give indications for the existence of an antagonistic modulation of high affinity alpha 2-adrenoceptors by the neuropeptide Y Y1 and neuropeptide Y Y2 receptor subtype in the nucleus tractus solitarii which may contribute to a reduction of alpha 2-adrenoceptor-mediated cardiovascular depression.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1994

Glial and neuronal glucocorticoid receptor immunoreactive cell populations in developing, adult, and aging brain.

A detailed mapping of glucocorticoid receptor (GR) immunoreactivity (IR) in rat CNS was performed employing a mouse monoclonal antibody against rat liver GR. Subjective comparisons were made between the present results and the available data in the literature. A semiquantitation of GR immunostaining was found necessary and was obtained by microdensitometric and morphometric techniques, which enabled the distinction of neuronal and glial cell populations containing GR IR in various CNS regions. GR IR in the CNS was mainly found in the nuclear compartment. The GR was present in neuronal populations with classical neurotransmitters, especially monoamines and glutamate and with various neuropeptides. The degree of colocalization varied according to the function of the brain area. Functional implications were made in relation to stress sensitivity, mood and nociception/antinociception. The global control of networks by glucocorticoids may allow an optimal integration of different types of circuits. The GR is found already in the fetal rat and the development of GR mRNA and receptor protein was followed during the pre- and postnatal periods. The GR appears to be a major factor in brain maturation and in modulation of stress responses. In aged Brown Norway rat brain GR IR but not mineralocorticoid receptor (MR) IR is reduced in the hippocampal nerve cells. The intensity of GR IR but not the number of nerve cells is altered, indicating a reduced activation of the GR in aging in this rat strain. Overall GR participates in neuronal plasticity from fetal and postnatal life to adult life and aging.

Aging↗
PubMed1994

Possible mechanisms for the powerful actions of neuropeptides.

In order to understand the mechanisms underlying the powerful actions of neuropeptides, the present article has emphasized the unique ability of neuropeptides to act as VT signals, which via high-affinity G-protein coupled receptors can exert long-lasting actions and control synaptic transmission via receptor-receptor interactions. Also of substantial importance is the ability of neuropeptides to act as a set of signals via the formation of different types of active fragments, which can act as negative-feedback or positive-feedback signals to modulate the response elicited by the parent peptide and to give origin to syndromic responses. Also in the actions of the fragments on the neuronal network, receptor-receptor interactions may play an important role both by modulating the parent peptide receptors and by modulating other types of VT and/or WT receptors. Future work will have to evaluate the role of neuropeptides as transcellular signals and as regulators of neuronal excitabilities after the formation of carbamates, but certainly new important developments are within the horizon of today's research.

Animals↗
PubMed1994

Evidence for an antagonistic angiotensin II/alpha 2-adrenoceptor interaction in the nucleus tractus solitarii.

Interactions between alpha 2-adrenoceptors and angiotensin II receptors were evaluated in the nucleus tractus solitarii of the rat by means of quantitative receptor autoradiography and cardiovascular analysis. In binding experiments using l-noradrenaline to compete for [3H]p-aminoclonidine binding sites, angiotensin II (1 nM) increased the IC50 value of l-noradrenaline by 50%. The angiotensin AT1 receptor antagonist, DUP753 (losartan), not only blocked this action but also decreased the IC50 value of l-noradrenaline. The modulatory effect of angiotensin II was also evaluated after addition of both DUP753 and PD123319, an angiotensin AT2 receptor antagonist, and counteraction of the reduction in the IC50 value of l-noradrenaline was observed. In saturation experiments angiotensin II increased the KD and Bmax values of [3H]p-aminoclonidine binding sites, compatible with possible uncoupling of the alpha 2-adrenoceptors. Cardiovascular analysis demonstrated that a threshold dose of angiotensin II (0.05 pmol) counteracted the vasodepressor effect produced by an ED50 dose of l-adrenaline, l-noradrenaline or clonidine coinjected in the nucleus tractus solitarii. DUP753 fully blocked this in vivo modulation of alpha 2-adrenoceptors by angiotensin II. These findings suggest the existence of an antagonistic angiotensin AT1/alpha 2-adrenoceptor interaction in the nucleus tractus solitarii. Therefore, it can be surmised that the activation of angiotensin II AT1 receptors may reduce the transduction of the alpha 2-adrenoceptors and thus the alpha 2-mediated vasodepressor responses.

Adrenergic alpha-Antagonists↗
PubMed1994

Generalized presence of a PEC-60-like peptide in catecholamine neurones.

PEC-60, a 60-residue intestinal peptide structurally related to the pancreatic secretory type of trypsin inhibitor, has been isolated, characterized and molecularly cloned. It shows biological activity as a hormone in both the gastrointestinal tract and in the immune system. We now report immunohistochemical evidence suggesting its neural localization exclusively within central and peripheral catecholamine (CA) neurones. PEC-60-like immunoreactivity was present in cell bodies, dendrites and nerve terminals of virtually all catecholamine neurones examined and including the noradrenergic gland cells of the adrenal medulla. PEC-60-like immunoreactivity was not seen, however, within the tyrosine hydroxylase-positive but CA-negative arcuate neurones producing growth hormone releasing hormone. The findings open up the possibility that a PEC-60-like peptide may represent a generalized co-transmitter in the peripheral and central CA neurones.

Animals↗
PubMed1994

Evidence for a regional distribution of hyaluronic acid in the rat brain using a highly specific hyaluronic acid recognizing protein.

By means of a highly specific hyaluronic acid-recognizing protein the localization and regional distribution of hyaluronic acid was demonstrated in the tel- and diencephalon and in the midbrain of the adult rat nervous system. Histochemistry revealed labeling associated with the plasma membrane in highly discrete nerve cell bodies of the frontoparietal cortex, the red nucleus, the zona reticulata of the substantia nigra, the oculomotor nucleus and the reticular thalamic nucleus. A strong labeling without association with perikarya was demonstrated in the subgranular zone of the dentate gyrus of the hippocampal formation. The present results open up the possibility that the hyaluronic acid found in high concentrations associated with some perikarya may have a special role in plasticity responses in these discrete nerve cell populations.

Animals↗
PubMed1994

On the regional distribution of heparan sulfate proteoglycan immunoreactivity in the rat brain.

By means of two monoclonal antibodies specific for heparan sulfate (HS)-related epitopes, one (10E4) against native HS chains and one (3G10) against desaturated uronates, a highly regional and differential distribution of these two epitopes have been observed in the adult rat brain. The 10E4 epitope immunoreactivity (IR) is mainly found in the substantia nigra, the red nucleus and the subgranular zone of the dentate gyrus, while the 3G10 epitope IR is mainly found in the CA2 area of the hippocampal formation and the pyramdial cells in the layer V of the frontoparietal cortex. The codistribution of both types of IRs with basic fibroblast growth factor (bFGF, FGF-2) in neurons and astroglia supports the notion that heparan sulfate proteoglycans (HSPG) in the extracellular matrix may serve as a site for storage of bFGF and assist in the bFGF-induced activation of the high-affinity FGF receptors linked to astroglia and neurons in these discrete areas.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗