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Biomedical subjects

G Alonso

Publications and source records attributed to G Alonso.

At least 127 records · Page 7Linked to original sources

The anterior periventricular hypothalamus is the site of somatostatin inhibition of its own release: an in vitro and immunocytochemical study.

The site of action of the inhibitory effect of somatostatin (SRIF) on its own release was studied by: (1) measuring SRIF release in vitro from tissue preparations containing either the proximal (periventricular hypothalamus) or the distal (median eminence) portions of the hypothalamic SRIF neurons, and (2) immunocytochemical investigation of the interconnections occurring between SRIF neuronal elements in these hypothalamic regions. In vitro, a biologically active, but noncross-reacting SRIF analog (D-Trp8 SRIF) in the RIA, inhibited 25 mM K+ induced SRIF release from anterior periventricular hypothalamic tissues. The inhibitory effect of D-Trp8 SRIF was dose-dependent, maximal at 10(-7) M, and restricted to this anterior region, since median-eminence SRIF release was not modified by the presence of D-Trp8 SRIF. Additionally, LHRH release from anterior periventricular hypothalamus was unchanged in the presence of D-Trp8 SRIF. In the periventricular nucleus, perikarya and dendrites of labeled SRIF neurons showed frequent apposition of their limiting membranes. Classical synapses were also observed between SRIF-containing axonal processes and labeled perikarya or dendrites. Although membrane appositions between neighboring SRIF axons frequently occurred in the median eminence, no synaptic-like SRIF-SRIF connections could be detected at this level. The data demonstrate a direct inhibitory action of a SRIF agonist on the anterior periventricular hypothalamic release of the peptide. This effect correlates well with the occurrence of SRIF-SRIF synapses in this region; suggesting that SRIF exerts a negative feedback in the control of its own release through autoreceptors located on the perikarya or dendrites of SRIF-containing neurons.

Animals↗

Reserpine inhibits release of vasopressin from the neural lobe of the pituitary in dehydrated rats.

The effects of reserpine on the osmotically induced release of pituitary vasopressin were studied (i) by measuring the urinary excretion and the vasopressin content of the neural lobe of pituitary, and (ii) by examining the ultrastructural morphology of axons in the neural lobe of dehydrated rats. After water deprivation for two days, control rats displayed characteristic antidiuretic response including a 75% reduction of urinary excretion and a six-fold decrease in vasopressin content of the neural lobe associated with a dramatic depletion of neurosecretory granules in corresponding axons. In contrast, when they received two dialy injections of reserpine, animals dehydrated for two days showed both urinary excretion and vasopressin contents in the neural lobe that remained at levels comparable to those measured in the normally hydrated rats. Additionally, neural-lobe axons of such dehydrated, reserpine-treated rats displayed a normal amount of neurosecretory granules. These data indicate that reserpine inhibits release of vasopressin from the neural lobe and favour the concept of a facilitatory role of the catecholaminergic innervation in the control of hypothalamo-neurohypophysial vasopressin-secreting neurons.

Animals↗

Electron microscopic immunocytochemical study of somatostatin neurons in the periventricular nucleus of the rat hypothalamus with special reference to their relationships with homologous neuronal processes.

The neurons containing somatostatin in the rat periventricular nucleus were studied by using a modified electron microscopic immunocytochemical technique that improves both the penetration of immunoreagents into unembedded immunostained tissues and the preservation of ultrastructural morphology. Inside perikarya and dendrites, immunostaining was not only associated with neurosecretory granules but also with ribosomes and saccules of the cis face of the Golgi apparatus. In the axonal profiles found in this region the labeling was observed both on neurosecretory granule cores and on the limiting membrane of small synaptic-like vesicles. Throughout the periventricular nucleus, both non-synaptic and synaptic relationships were shown between labeled neurons. Non-synaptic relationships mainly consisted of direct apposition of the membranes of neighboring neurons by dendrosomatic, somasomatic or dendrodendritic contacts. These labeled perikarya and dendrites were also synaptically contacted by labeled axonal endings containing numerous aggregated synaptic-like vesicles. The physiological significance of the synaptic and non-synaptic relationships between somatostatinergic neurons is discussed in terms of possible synchronization between homologous neurons of the somatostatin neuroendocrine system and control of these neurons by a central ultra-short loop feedback mechanism.

Animals↗

Diurnal-stimulated and stress-induced ACTH release in rats is mediated by ventral noradrenergic bundle.

Female rats were bilaterally injected with 3 micrograms of 6-hydroxydopamine (6-OHDA) dissolved in 0.2 microliter saline, via a glass micropipet stereotaxically implanted into the ventral noradrenergic-ascending bundle (VNAB). This bundle conveys most of the catecholaminergic innervation to the paraventricular nuclei and originates from the locus coeruleus and from two medullary groups of neurons (A1 and A2). Two weeks after injection, and 1 wk after the subsequent implantation of an arterial cannula, serial blood samples were taken from each rat over a 36-h period for assay of basal secretion patterns of ACTH and corticosterone (C) by radioimmunoassay and radiocompetition, respectively. Other blood samples were collected at short intervals over a 2-h period to explore the stress-ether responses of both hormones. Effects of 6-OHDA injections on catecholaminergic innervation were attested by the striking decrease in the histofluorescence of hypothalamic catecholamines and by the 86% drop in the hypothalamic noradrenaline concentrations measured by high-performance liquid chromatography at constant dopamine titers. Compared with control, sham-lesioned rats, pharmacological destruction of the VNAB by 6-OHDA led to 1) obliteration of the circadian patterns for ACTH and C and the emergence in their place of ultradian fluctuations of reduced amplitude above base-line levels and 2) 80% inhibition of the ACTH stress response which correlated with a short-lived, depressed C response. These results are discussed within the framework of the controversial literature on the mechanisms by which catecholamines may control corticotropic function.

Adrenocorticotropic Hormone↗

Lung inhalation scintigraphy: development of a new aerosol system.

A new technique for lung inhalation scintigraphy is reported, developing a new aerosol system, based on the original system of Taplin [1]. With two small compact polypropylene reservoirs, this 99Tcm DTPA technique allowed continuous breathing during the inhalation period. This system proved to be a useful alternative to that using radioactive gases and the system of Taplin, due to its low cost and the ease with which several projections may be obtained.

Adult↗

Ultrastructural analysis of the noradrenergic innervation of rat supraoptic nucleus.

The noradrenergic innervation of the rat supraoptic nucleus (SON) was examined by high resolution radioautography after animals had been intracerebrally injected with [3H]noradrenaline (NA). In the medial portion of the SON, noradrenergic varicosities were scattered throughout this nucleus, but were preferentially concentrated in its ventral subdivision. 25.5% of these NA varicosities displayed typical synaptic contacts, with either the somatic or proximal dendritic portions of neurosecretory neurons (9.2%) or with small dendritic processes of such neurons (16.3%). The possibility is discussed that at least some of the dendritic NA synapses detected in the ventral subdivision of the SON, which preferentially contains vasopressinergic perikarya, may affect the neurosecretory neurons located in the dorsal part of this nucleus, which preferentially contains oxytocinergic perikarya.

Animals↗

[Demonstration of pulsatile secretion of somatostatin in the third cerebral ventricle of unanesthetized rats].

Using a specially designed push-pull cannula stereotaxically implanted into the 3rd ventricle, a pulsatile secretion of IR-SRIF with a circhoral periodicity was detected in male rats. At 30 min. to 1 h 1/2 intervals the secretion rate of the neuropeptide rose from a baseline rate of 14.5 +/- 0.5 pg/10 min., corresponding to a baseline concentration of 60 +/- 2 pg/ml to peaks of 50 +/- 5 pg/10 min. or 210 +/- 22 pg/ml, respectively. This pulsatile pattern was restricted to rats where histological examination showed no dilation pictures of the ventricle. The possible origin and function of intra-ventricular IR-SRIF are discussed.

Animals↗

Retrograde axoplasmic transport of neurosecretory material. An immunocytochemical and electron-microscopic study of transected axons in normal and colchicine-treated rats.

The axonal transport of neurosecretory material was studied in neurosecretory axons of the supraoptico-posthypophyseal system after in-situ transection of the median eminence. Two hours, 8 h, and 18 h after the lesion, both vasopressin and oxytocin antibodies revealed progressive accumulations of immunoreactive material not only in the proximal but also in the distal stumps of the transected axons. The electron-microscopic examination of these axonal portions revealed that such intense immunopositive labelings could be correlated, in both stumps, to a conspicuous accumulation of neurosecretory granules. It is concluded that, under normal physiological conditions, a significant amount of axoplasmic neurosecretory material is transported in retrograde direction and that such a retrograde transport mainly involves neurosecretory granules.

Animals↗

CNS control of the circadian adrenocortical rhythm.

The effects of various CNS impairments on the circadian rhythm of plasma ACTH and Corticosterone (C) were studied in individual cannulated female Sprague-Dawley rats. Pinealectomy had no effect whatever the light perception (intact or blinded rats). Bilateral ablation of paraventricular nuclei did not obliterate the hormonal rhythms, although the rhythms' amplitude were markedly depressed. On the other hand, destruction of suprachiasmatic nuclei (SCN) or systemic blockade of the serotoninergic (5-HT) system by pCPA blocked ACTH rhythm at baseline levels, although circadian or ultradian fluctuations with normal amplitudes persisted for C. Similar effect was observed in several blinded rats with raphe lesions suppressing 5-HT innervation of SCN. Daily 5-HTP injections, if given 4 h after dawn restored normal ACTH rhythm. The respective role of related structures in the rhythms' control will be discussed.

Adrenal Cortex↗

Tumor-associated changes in plasma samples revealed by two-dimensional macromolecular mapping and selective lectin binding.

Two-dimensional electrophoretic analysis of plasma samples from EL-4 lymphoma-bearing C57 black mice revealed five 75 kd protein species in contrast with the presence of only two comparable components of similar migration in plasma from control animals. In contrast, no comparable alterations were observed in a comparison of plasma samples from L1210 tumor-bearing DBA mice and the corresponding plasma from animals immune-suppressed with antilymphocytic serum or in control plasma from DBA control plasma from DBA control animals. Analysis of selective binding using iodinated lectins revealed significant binding of I125 Lens culinaris in the more cathodic 75 kd component present in the plasma from control C57 black mice and a decreased Lens culinaris binding in the corresponding plasma components from EL-4 tumor-bearing C57 black animals. An identical assay with the same samples using I125 Ricinus communis did not show significant interaction with any 75 kd protein species, revealing instead lectin binding in components with molecular weights of about 70 and 50 kd. Our results suggest the use of combined two-dimensional electrophoretic separation and relative lectin binding in the analysis of tumor-specific and tumor-associated changes in plasma samples from tumor-bearing individuals.

Animals↗

[Synthesis, cytostatic activity and mechanism of action of N-glycosylhalomethylazoles. A new class of alkylating agents].

A model to produce a new type of alkylating agents having anti-cancer activity is described. They consist of a halomethyl-azol group of the benzyl type as alkylating center, and a sugar moiety as a carrier fragment. Alkylating nucleosides were produced as halomethyl-pyrazole, -imidazole, 1.2.3-triazole, and 1.2.4-triazole derivatives following the model, and tested upon Ehrlich ascites cancer and P-388 lymphocytic leukemia.

Alkylating Agents↗