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Adrenergic innervation of cat adrenal medulla.

Cat adrenal medulla was studied to determine whether or not an adrenergic nerve supply was available to medullary cells. The techniques used were those of routine electron microscopy, injection and uptake of "false" transmitter substance (5-hydroxydopamine), injection of 6-hydroxydopamine, which selectively destroys postganglionic adrenergic elements and a specific cytochemical method using glutaraldehyde and heavy metal techniques for cytochemical localization of biogenic amines. Each method consistently demonstrated adrenergic fibers and terminals in the adrenal medulla; these adrenergic elements contain dense, large core and small core vesicles which are not of the "dense cored" cholinergic type. Localization of adrenergic fibers and terminals is deemed significant since the latter had the bouton en passage configuration immediately adjacent to norepinephrine cells; adrenergic elements were not seen in close relationship to epinephrine cells. Consistency of the findings from the three techniques point to the fact that the norepinephrine cells of the adrenal medulla have a dual innervation, both cholinergic and adrenergic. This type of innervation pattern is not unique for the autonomic nervous system, but it has not been reported previously for adrenal medullary cells. It is believed that such an innervation pattern has functional and pharmacologic significance.

Adrenal Medulla↗

Intracerebral adrenal medulla grafts: a review.

This review summarizes basic and clinical research on intracerebral adrenal medulla grafts, emphasizing potential applications to Parkinson's disease. Properties of intraventricular and intraparenchymal grafts are described, and cell survival and functional effects are compared. It is clear that adrenal medulla allografts survive poorly in the parenchyma of the corpus striatum and better in the lateral ventricle. Nerve growth factor (NGF) may improve the survival of adrenal medulla grafts. In the absence of added NGF even adrenal medulla grafts in the ventricle survive irregularly, and the factors required for graft survival in the ventricle are not well understood. In the 6-hydroxydopamine-lesioned rat model most evidence suggests, not surprisingly, that adrenal medulla grafts produce functional effects only when they survive. These effects may be related to production of catecholamines by the transplanted cells. In addition, adrenal medulla grafts may produce trophic effects on host brain. These effects are most evident in animals with MPTP-induced damage to dopaminergic systems and may be nonspecific, possibly related in part to the brain injury that is induced by graft implantation. Trophic effects may contribute to the functional effects of adrenal medulla grafts: For intraparenchymal grafts, trophic effects that do not require cell survival may contribute small functional changes, while additional behavioral effects may require substantial chromaffin cell survival. The evidence for direct dopamine-mediated effects as compared to trophic mechanisms of action for these grafts in animal models for Parkinson's disease is presented. Clinical studies of adrenal medulla grafts in human patients are examined and compared in detail. When inspected closely, the various clinical studies are in general agreement on most points, although there are differences in the degree of improvement found, both across different studies and individual patients. It is concluded that some beneficial clinical effects occur, with small to modest changes in most patients and substantial improvement in a minority of patients. There also seem to be larger or more consistent changes in durations of "on" and "off" times in L-dihydroxyphenylalanine-treated patients. There are substantial side effects, and it is not clear that the clinical changes are sufficient to justify performing adrenal medulla transplantation in human patients as a routine procedure.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Medulla↗

Gastrin secretion from human antral G cells in culture.

Receptor-dependent and -independent regulation of gastrin secretion from cultured human antral G cells was investigated. Human antral mucosal cell preparations that were enriched for G cells were obtained by sequential incubations with collagenase and ethylenediaminetetraacetic acid, centrifugal elutriation, and short-term culture. After a 2-day incubation period, gastrin- and somatostatin-containing cells accounted for 15% and 5%, respectively, of the total adhered-cell population. Forskolin, A23187, and beta-phorbol 12 myristate 13-acetate stimulated basal gastrin secretion from cultured human G cells in a concentration-dependent fashion. These results indicate that gastrin release could be mediated by elevations in cytosolic cyclic adenosine monophosphate levels, calcium influx, or activation of protein kinase C. A direct stimulatory role for bombesin- and gastrin-releasing peptide was supported by experiments showing concentration-dependent enhancement of gastrin release by bombesin from 0.01 fmol/L to 10 nmol/L. The putative bombesin antagonist [Leu13-psi-CH2NH-Leu14] bombesin augmented basal gastrin levels by itself and produced weak inhibition of bombesin-induced gastrin secretion from human antral G cells. Somatostatin potently suppressed forskolin- and bombesin-mediated gastrin release but did not significantly alter basal gastrin levels. These results suggest that bombesin and somatostatin directly activate and inhibit G-cell function via specific and sensitive receptors. Furthermore, the adenylate cyclase and phosphatidyl inositide second messenger systems seem to be intracellular mediators of gastrin secretion from human antral G cells.

Bombesin↗

Neurochemical, electrophysiological and immunocytochemical evidence for a noradrenergic link between the sympathetic nervous system and thymocytes.

The object of these experiments was to investigate whether noradrenaline is the signal neurotransmitter between the sympathetic nervous system and rat thymocytes. Using immunocytochemistry, evidence was obtained that the rat thymus (thymic capsule, subcapsular region and connective tissue septa) is innervated by noradrenergic varicose axons terminals (tyrosine hydroxylase- and dopamine-beta-hydroxylase-immunostained nerve fibres). This innervation is mainly associated with the vasculature and separately from vessels along the thymic tissue septa it branches into the thymic parenchyma. Using electron microscopy, classical synapses between thymocytes and neuronal elements were not observed. The neurochemical study revealed that these nerve terminals are able to take up, store and release noradrenaline upon axonal stimulation in a [Ca2+]o-dependent manner. The release was tetrodotoxin (1 microM)-sensitive, and reserpine pretreatment prevented axonal stimulation to release noradrenaline, indicating vesicular origin of noradrenaline. In addition, it was found that the release of noradrenaline was subjected to negative feedback modulation via presynaptic alpha 2-adrenoreceptors. Using a patch-clamp technique, electrophysiological evidence was obtained showing that noradrenaline inhibits in a concentration-dependent manner outward voltage-dependent potassium (k+) current recorded from isolated thymocytes. Since noradrenergic varicose axon terminals enter the parenchyma thymocytes and the boutons are not in close apposition to their target cells, noradrenaline released from these terminals diffuses away from release site to reach its targets, thymocytes, and to exert its inhibitory effect on voltage-dependent K+ -current. Since K+ channels are believed to be involved in T cell proliferation and differentiation, the modulation of K+ channel gating by noradrenaline released in response to axonal activity suggests that signals from blood-born or locally released hormones and cytokines. In this respect, noradrenaline released from non-synaptic neuronal varicosities and exerting its effect within the radius of diffusion may serve as a chemical link between the sympathetic nervous system and thymocytes and may have physiological and pathological importance in the thymus during stress and inflammatory/immune responses.

Adrenergic alpha-Antagonists↗

On the adrenergic system of ganoid fish: the Florida spotted gar, Lepisosteus platyrhincus (Holostei).

Falck-Hillarp fluorescent histochemistry, analyses of catecholamine content in different organs and experiments with drug effects on isolated strip preparations were used to study the adrenergic system of the Florida spotted gar, Lepisosteus platyrhincus. The study reveals a well developed system of adrenergic nerve terminals, especially in blood vessels and in the wall of the sinus venosus and atrium. The lung (swimbladder) receives an excitatory cholinergic nerve supply which controls both smooth and striated muscle in the trabeculae of the lung. No conclusive evidence for an adrenergic inhibitory innervation of the lung was obtained. Chromaffin cells line the walls of the posterior cardinal veins, similar to the situation in the teleosts, and the dominating catecholamine in the chromaffin tissue and in the blood plasma is adrenaline. The concentration of adrenaline in the blood plasma is high enough to affect the contraction force of the heart, and circulating adrenaline may thus contribute to the adrenergic control of the heart in this species.

Adrenergic Fibers↗

[Clinico-neurohumoral interrelationships in neuroses].

The paper is related to studies of the sympathico-adrenal activity, hypophysisadrenal and entero-chromaphine systems in patients with hysterical and phobic neuroses. They detected certain regularities in the initial activities of these systems as well as of their reactivity depending upon the character of the functional symptom, psychological personality traits and cerebral dysfunctions.

17-Hydroxycorticosteroids↗

Apoptosis in the adrenal gland of non-obese diabetic (NOD) mice.

Apoptosis appears to play an important role in the development of diabetes in the non-obese diabetic (NOD) mouse. Since the autoimmune process leading to the manifestation of insulin dependent diabetes mellitus (IDDM) can also affect the sympathochromaffin system, we analyzed the role of apoptosis and infiltration of the adrenal medulla as features of this autoimmune process in parallel with the development of diabetes. Prediabetic and diabetic NOD mice aged 3 to 30 weeks were studied and compared with control mice. Apoptosis was assessed by in situ end-labeling method and ultrastructural analysis. Adrenals were screened for lymphocytic infiltration by conventional hematoxylin-eosin staining. Chromaffin cells were characterized by immunohistochemical staining against synaptophysin and tyrosine hydroxylase. Apoptotic nuclei were detected in all mice studied at a very low level, mainly occuring within the connective tissue between medulla and cortex. The maximum score was achieved at 3 weeks (1.91+/-0.48 apoptotic cells/1000 counted cells; n = 4). There was no significant difference between NOD mice and control mice. No correlation could be found between blood glucose levels and apoptosis. On the ultrastructural level, apoptotic cells presented typical features of apoptosis, i.e. condensed nuclei and cytoplasm. Neither in NOD mice nor in controls lymphocytic infiltration or fibrosis of the adrenal was detected. Even NOD mice with overt diabetes did not exhibit morphological signs of medullitis. In summary, no signs of immune destruction of the adrenal medulla in NOD mice aged 3 to 30 weeks could be detected.

Adrenal Cortex↗

Membrane fusion protein synexin (annexin VII) as a Ca2+/GTP sensor in exocytotic secretion.

Exocytotic membrane fusion and secretion are promoted by the concerted action of GTP and Ca2+, although the precise site(s) of action in the process are not presently known. However, the calcium-dependent membrane fusion reaction driven by synexin (annexin VII) is an in vitro model for this process, which we have now found to be further activated by GTP. The mechanism of fusion activation depends on the unique ability of synexin to bind and hydrolyze GTP in a calcium-dependent manner, both in vitro and in vivo in streptolysin O-permeabilized chromaffin cells. The required [Ca2+] for GTP binding by synexin is in the range of 50-200 microM, which is known to occur at exocytotic sites in chromaffin cells, neurons, and other cell types. Previous immunolocalization studies place synexin at exocytotic sites in chromaffin cells, and we conclude that synexin is an atypical G protein that may be responsible for both detecting and mediating the Ca2+/GTP signal for exocytotic membrane fusion.

Animals↗

Thyroid hormones and nervous system development.

Regulation by hormones of nervous system development is well recognized in humans, laboratory animals and cultured nerve cells. Thyroxine (T4) and triiodothyronine (T3), the major thyroid hormones, act on brain development and maturation by binding to T3 nuclear receptors. T3 responsive genes have been identified with the T3 receptor as a superfamily of genes including cortisol and estrogens, necessary for adaptation and survival. Less defined are T3 and T4 actions on the peripheral nervous system. In chromaffin cells explanted from the adrenal of immature rats, T3 induces the enzyme tyrosine hydroxylase, involved in catecholamine synthesis. This action is similar but, so far, apparently independent from Nerve Growth Factor promotion of sympathetic and chromaffin cell growth. Mechanisms based on nuclear binding depend on multiple receptors functionally diversified; their selectivity of action over a wide range of early and late developmental patterns is an attractive hypothesis to be further explored.

Animals↗

[Biogenic amines in endocrine cells producing polypeptide hormones. The APUD-cells (Pearse) (author's transl)].

APUD-cells (A = Amine, P = Pprecursor, U = Uptake, D = Decarboxylation) are endocrine cells with numerous common characteristics: 1. They produce polypeptide hormones of low molecular weight. 2. They possess specific 1-amino acid decarboxylases to synthesize catecholamines and/or 5-hydroxytryptamine from precursors. 3. A part of the APUD-cell family primarily accumulates biogenic amines within their cytoplasm. 4. All APUD-cells are rich in specific secretory granules that are the morphological substrate for most of their common features.--Enzyme histochemically the APUD-cells represent a rather heterogenous population. The capacity to take up biogenic amines from the blood is confined to a smaller numer of APUD-cells. The concept of the APUD-cells representing a peripheral neurosecretory system (Pearse und Polak, 1971) appears to be premature. It is probable that in several APUD-cells the accumulation of biogenic amines only constitutes a phenomenon without any physiological relevance which, notwithstanding, could explain pathological reactions of APUD-cells.

Animals↗

A solitary functioning osseous metastasis from a malignant pheochromocytoma of the organ of Zuckerkandl.

A case of a malignant phenochromocytoma of the organ of Zuckerkandl is reported. There was a solitary functional metastasis in the left femur, which was treated by hip disarticulation after removal of the primary. The patient is asymptomatic and free of further metastases after 3 years. Other reported cases of solitary metastases from malignant pheochromocytomas are cited. These occurred most frequently in the skeleton system, which is the most common site of distant metastases in malignant pheochromocytoma. The reported case and the review of the literature indicate that solitary or limited metastatic lesions should be treated surgically by partial or, when possible, complete resection.

Adolescent↗

Developmental expression of serotonin-like immunoreactivity in the sympathoadrenal system of the chicken.

The avian sympathoadrenal system has been used as a model to examine the differentiation of cells expressing neuroactive substances derived from the neural crest. Previous studies have dealt with the expression of the "classical" neurotransmitters acetylcholine and catecholamines and of the neuropeptides somatostatin and vasoactive intestinal polypeptide. We have used immunocytochemistry to examine the developmental expression of the monoamine serotonin (5HT) in the chicken sympathoadrenal system. 5HT-like immunoreactivity (5HT-LI) was found to be transiently expressed by cells of the sympathetic ganglia very early in development (E-5 to E-8), disappearing almost entirely at more advanced embryonic stages (E-10 to E-19) and post-hatched chickens where only a population of cells similar to mammalian small intensely fluorescent cells express immunoreactivity to the amine. In contrast, in the adrenal gland of embryos and post-hatched chickens, most chromaffin cells also express 5HT-LI. Double labeling experiments show that in both the adrenal gland and the sympathetic ganglia catecholaminergic properties and somatostatin immunoreactivity are co-expressed with 5-HT-LI. Moreover, the cells that transiently express 5HT-LI in sympathetic ganglia also transiently express somatostatin. The catecholaminergic cells expressing serotonin and somatostatin appear to define a biochemical phenotype common to some chromaffin cells, small intensely fluorescent cells and early sympathoblasts.

Adrenal Glands↗

Ultrastructural and histochemical observations of neuroendocrine granules in nonneoplastic ovaries.

Argyrophil and argentaffin cells are rarely seen in female genital tract structures. Their presence in normal, apparently healthy ovaries has not been reported until the present observation. Histochemical and ultrastructural studies demonstrated cells within the ovaries of two nonpregnant patients in the reproductive age that belong to the neuroendocrine or amine precursor uptake and decarboxylation (APUD) system. The lack of other discernible pathologic conditions suggests that these cells may be normal cellular constituents within the ovaries and lends support to the belief of a neural crest origin for primary ovarian carcinoid not associated with teratomatous or mucinous elements.

APUD Cells↗

[The intraneural endocrine cell--the starting point of the origin of carcinoid tumors?].

Endocrine cells are demonstrable by electron microscopy in the lamina propria of the appendix mucosa. They are always in direct contact with a nerve fibre. The endocrine cell (types EC1, and EC2) and the polyaxonal non-myelinated nerve fibres are separated from the interstitial connective tissue by a common continuous basal lamina. The term "ECZ-NF complex" is suggested by the author to describe this morphological and functional unit. The intraneural endocrine cells may be derived from neuroendocrine-programmed ectoblasts according to Pearse (1977). These intraneural endocrine cells may comprise an additional extraepithelial cellular part of the "diffuse neuroendocrine system". The electron microscopic demonstration of similarly structured "eZ-NF complexes" (polypeptide-producing endocrine cell and nerve fibre) in connection with the demonstration of small nerve fibres within carcinoids of appendix, caecum and rectum allows us to propose a hypothetical pathogenesis of gastrointestinal carcinoids from these intraneural endocrine cells.

Appendix↗

Multicompartmental secretion of ascorbate and its dual role in dopamine beta-hydroxylation.

The neurobiological functions of ascorbate have both intra- and extracellular sites of action. Intracellularly, it participates predominantly in enzymic and transport reactions for neurotransmitter and hormone biosynthesis. Ascorbate is the cofactor for the dopamine beta-hydroxylase and peptidylglycine alpha-amidating monooxygenase systems, which catalyze the synthesis of norepinephrine and a variety of alpha-amidated peptides, respectively. The localization of these enzymes within the neurotransmitter- or hormone-containing storage vesicle requires a system for the constant regeneration of ascorbate to the reduced form. In fact, ascorbate participates in its own regeneration as a component of the vesicular electron-transport system. In addition to the roles of ascorbate in messenger synthesis, it is secreted from cells from different subcellular compartments. The extracellular role(s) of ascorbate are still unknown, although its interaction with and modification of plasma membrane proteins suggests some modulatory function.

Adrenal Medulla↗

[APUD system and neuroendocrine tumors ("apudomas")].

Current concepts of the APUD-system combining neuroendocrinal cells located in different organs are presented. The main feature of these cells is the capacity to accumulate precursors of biogenic amines, to decarboxylate them and to produce biogenic amines or polypeptide hormones. The problem of the development of tumours of these cells is discussed, and their morphological, histochemical and clinical features are described.

Biogenic Amines↗

[Structural basis of neurohormonal control of gastric secretory activity].

Distances between neural, endocrinal and working cells in the gastric wall tissue do not exceed some hundreds nm, i. e. they are within limits of the physiological parameters for the effect of biologically active substances diffusely spreading along the interstitium. A structural scheme of the neurohormonal regulatory mechanism is suggested, basing on the author's data and those of the literature. Combination of producer-mediator-cells and target-cells united by the interstitial gap, along which biologically active substances are transported, serves as its base. Mast cells--mobile endocrinic glands--and neural terminals of various modality may serve as a source for changing the modulatory tonus in the given tissue area. The cells producing mediators (neural and endocrine) are, in their turn, target-cells for other biologically active substances getting into the interstitium. The whole structure can be compared with the synaptic system, where the membranes of the producer-mediator-cells serve as the presynaptic pole, while the membranes of the target-cells play the role of the postsynaptic pole. The interstitial gap performes the part of the synaptic gap. In this peculiar diffuse synapse, the membranes of neural and endocrine cells serve as pre- and postsynaptic membranes simultaneously.

Animals↗

Quantification of enterochromaffin cells with serotonin immunoreactivity in the duodenal mucosa in coeliac disease.

Enterochromaffin cells in the duodenal mucosa were stained by using a monoclonal antibody against serotonin immunoreactive sites and an indirect immunoperoxidase technique. A semi-automatic image analysing system showed increased numbers of these cells in patients with untreated coeliac disease compared with a control group. The number of serotonin positive granules in individual enterochromaffin cells also seemed to be increased in patients with coeliac disease, a finding which may be related to the pathogenesis of this disorder.

Adolescent↗