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At least 379 records · Page 21Linked to original sources
PubMed2002

Exocytosis: the chromaffin cell as a model system.

Neurons and neuroendocrine cells release transmitters and hormones by exocytosis of secrctory vesicles or granules. Among the cell models that have provided insight into the molecular machinery underlying the successive steps of exocytosis, adrenal chromaffin cells have taken a prominent place. Thus, most of the molecular players that orchestrate the formation, targeting, docking, and fusion of secrctory granules have been identified in chromaffin cells. By offering the opportunity to combine the use of recent biophysical techniques allowing single-vesicle resolution and specific biochemical modifications in the protein machinery involved in exocytosis, chromaffn cells remain a powerful model to address new and still open questions in the field of secretion.

Actins↗
PubMed1990

Angiotensin II and angiotensin converting enzyme binding in human adrenal gland and pheochromocytomas.

Binding sites for angiotensin II (Ang II) and angiotensin converting enzyme (ACE) were studied by autoradiography in human, rat and bovine adrenals and human pheochromocytomas. In human and rat adrenals, binding sites for both Ang II and ACE were found in the medulla and zona glomerulosa. In bovine adrenals, ACE binding sites were not detectable, while Ang II binding was higher in the zona glomerulosa, lower in the rest of the cortex and undetectable in the medulla. In pheochromocytomas, ACE binding was homogeneously distributed, but no Ang II binding was detected. These results suggest that circulating and/or locally formed Ang II could regulate adrenomedullary and zona glomerulosa functions in man, and show that chromaffin cells in tumors retain ACE binding sites but lose Ang II binding sites. Thus, there are alterations in the regulation of the renin-angiotensin system in chromaffin tumors.

Adrenal Gland Neoplasms↗
PubMed1981

Release of immunoreactive serotonin into the lumen of the feline gut in response to vagal nerve stimulation.

Immunoreactive serotonin was detected in the lumen of the proximal jejunum of food-deprived cats. During perfusion of this intestinal segment in vivo, there was a constant basal rate of intraluminal secretion of this amine. The rate of secretion was significantly increased during efferent electrical stimulation of the cut cervical vagal nerves. This stimulatory effect was not altered after bilateral adrenalectomy was performed in the same animals. A synchronous release of substance P into the gut lumen was also demonstrated during vagal stimulation. During the period of increased intraluminal secretion of immunoreactive serotonin, there was no demonstrable change in the portal or systemic blood levels of this amine.

Adrenalectomy↗
PubMed1975

Effects of guanethidine on paraganglionic cells in the superior cervical ganglion of the rat.

Paraganglionic cells in the rat superior cervical ganglion were investigated by fluorescence and electron microscopy following treatment with guanethidine for 5-30 days. Control animals received saline and guanidine. Fluorescence cytophotometric measurements revealed a general decrease in the catecholamine content of paraganglionic cells in guanethidine-treated animals. However a few cell clusters showed focal increases. Similarly by electron microscopy there was a general decrease of cell clusters showing increases. -- guanethidine -- as well as guanidine--treated animals showed non-specific cytological alterations such as mitochondrial swelling and increase of cytoplasmic glycogen. However no changes of catecholamine contents and of dense core vesicles were noted in control animals. These results confirm the conception that in rat paraganglionic cells the dense core vesicles are the main storage site of catecholamines. The marked difference in the response of some cell culsters to the experimental treatment can be considered as evidence of functional heterogeneity of this cell population in the rat superior cervical ganglion.

Animals↗
PubMed1993

[Calcium-dependent regulated secretion is controlled by GTPase Rab3 in neuroendocrine cells].

Changes in intracellular free calcium concentration ([Ca2+]i) play a fundamental role in the regulation of hormone secretion by endocrine and neuronal cells. The increase in [Ca2+]i is one of the principle events in stimulus-secretion coupling. Secretory phenomena are subjected to modulation via a large number of intracellular factors which can act on vesicular transport, exocytosis or endocytosis. Among these factors are proteins able to bind and hydrolyse the nucleotide GTP belonging to the ras superfamily of small GTPases (or superfamily of small G proteins). GTPases of the Sec4/Ypt1/Rab family have been implicated in the regulation of intracellular vesicle traffic. A role for Rab3 in regulating secretion was initially proposed because of its specific expression in the nervous and endocrine systems, and its association with secretory vesicles. The function of Rab3 has been studied in two types of neuroendocrine cells: the anterior pituitary lactotroph cells and the adrenal medulla chromaffin cells. Two techniques were combined: intracellular injection of antisense oligonucleotides and recombinant proteins, followed by membrane capacitance measurements. The inhibition of Rab3b synthesis in lactotroph cells by antisense oligonucleotides provokes an inhibition of exocytosis. On the other hand, injection of antisense oligonucleotides directed against rab3a into chromaffin cells led to a stimulation of the secretory response to successive depolarizations of the cell membrane. These results indicate that Rab3 proteins control the calcium-dependent secretory process in neuroendocrine cells. In lactotroph cells Rab3b seems to play a stimulatory role, whereas Rab3a acts as a negative regulator of catecholamine release in chromaffin cells.

Animals↗
PubMed1982

[Experimental model with the additional source of endogenous serotonin].

The only experimental approach to the increase in the body serotonin level is a pharmacological one that has a number of shortcomings. The authors suggest an experimental model with additional source of endogenous serotonin (ASS-model) which occurs after embryonal gastrointestinal tract transplantation beneath the skin of adult syngeneic mice. The developing transplants showed significant amounts of serotonin and serotonin-producing enterochromaffin cells. The ASS-model provides long-term and selective increase in the blood serotonin content (by 40% on the average) with no changes being detected in the brain. This model may be used for studies on the role of serotonin in peripheral regulation of the physiological systems.

Animals↗
PubMed1975

[5-Methoxy-N-acetyltryptamine (melatonin) in enterochromaffin cells].

As evidenced from the action of acetone extracts of the mucous layer of the human appendix, these extracts contain a substance capable of bleaching the frog's skin. Model experiments with 0.1% adrenaline, 0.2% noradrenaline, 2.5% hydrocortisone and solutions of various concentrations of synthesized melatonin permitted to identify the above substance as melatonin. The bleaching aciton dependence on the number of enterochromaffin cells (Ec-cells) in the mucous layer of the appendix, and the presence of serotonin in Ec-cells reveal a connection between melatonin and Ec-cells. An average content of 5-methoxy-N-acetyltryptamine in the human appendix amounts to 0.004 mg per 100 Ec-cells. It is suggested that the epiphysis and enterochromaffin cells compose a common functional neuroendocrine system playing a definite role in maintaining the homeostasis of the organism.

Animals↗
PubMed1980

Catecholamines in paraganglionic cells of the rat superior cervical ganglion: functional aspects.

In the rat SCG two types of paraganglionic cells have been identified immunohistochemically in a ratio of about 5% DBH-positive to 95% DBH-negative cells. Measurements of CAs in SIF cell clusters separated from principal neurons with the microlaser and using the technique of quantitative mass fragmentography disclosed the presence of E within paraganglionic cells, thus confirming the proposal that, besides DA, E also is stored in most cells. Following immobilization of adult rats, the majority of SIF cells revealed a time-dependent loss of formaldehyde-induced fluorescence intensity that could be ultrastructurally correlated with an increasing degranulation of small granule-containing perikarya, presumed to store DA and E. Similar results were obtained in type I cells of the rat carotid body and adrenal medullary cells, thus suggesting a mutual endocrine function. An additional interneuronal mode of modulation is assumed, since degranulated cells are capable of displaying efferent synaptic contact with postganglionic neurons. A minor cell population, storing granular vesicles similar to those in the NE-containing cells of the adrenal medulla, did not respond with degranulation to functional strain of the vegetative nervous system. Our results strongly corroborate the hypothesis that a functional dualism exists: Most paraganglionic cells can act as an interneuron and as an endocrine cell.

Animals↗
PubMed1988

Direct relationship between mononuclear leukocyte and lung beta-adrenergic receptors and apparent reciprocal regulation of extravascular, but not intravascular, alpha- and beta-adrenergic receptors by the sympathochromaffin system in humans.

To examine putative relationships between adrenergic receptors on accessible circulating cells and relatively inaccessible extravascular catecholamine target tissues, we measured mononuclear leukocyte (MNL) and lung beta-adrenergic receptors and platelet and lung alpha-adrenergic receptors in tissues obtained from 15 patients undergoing pulmonary resection. Plasma catecholamine concentrations were measured concurrently to explore potential regulatory relationships between the activity of the sympathochromaffin system and both intravascular and extravascular adrenergic receptors. MNL and lung membrane beta-adrenergic receptor densities were correlated highly (r = 0.845, P less than 0.001). Platelet alpha 2-adrenergic receptor and lung alpha 1-adrenergic receptor densities were not. Lung alpha 1-adrenergic receptor densities were positively related to plasma norepinephrine (r = 0.840, P less than 0.01) and epinephrine (r = 0.860, P less than 0.01) concentrations; in contrast, lung beta-adrenergic receptor densities were not positively related to plasma catecholamine concentrations (they tended to be inversely related to plasma norepinephrine and epinephrine [r = -0.698, P less than 0.05] levels). This apparent reciprocal regulation of alpha- and beta-adrenergic receptors by the sympathochromaffin system was only demonstrable with adrenergic receptor measurements in the extravascular catecholamine target tissue. Neither MNL beta-adrenergic receptor nor platelet alpha-adrenergic receptor densities were correlated with plasma catecholamine levels. Thus, although measurements of beta-adrenergic receptors on circulating mononuclear leukocytes can be used as indices of extravascular target tissue beta-adrenergic receptor densities (at least in lung and heart), it would appear that extravascular tissues should be used to study adrenergic receptor regulation by endogenous catecholamines in humans. These data provide further support for the concept of up regulation, as well as down regulation, of some adrenergic receptor populations during short-term activation of the sympathochromaffin system in humans.

Adult↗
PubMed1975

Neurohumoral mechanisms in hypertension.

Neurohumoral mechanisms operating via the catecholamines are discussed in their relationship to such hypertensive diseases as pheochromocytoma and labile and established essential hypertension. 2. In pheochromocytoma, diagnosis depends almost entirely on identification of increased amounts of catecholamine metabolites in the urine. Because of the danger, manipulative or invasive procedures both for diagnosis and during surgery should be kept at a minimum. 3. In established essential hypertension, reactivity to norepinephrine and plasma norepinephrine are increased, whereas norepinephrine uptake and apparent secretion rate are decreased. 4. In labile essential hypertension, reactivity to epinephrine and probably plasma epinephrine are increased and uptake of epinephrine decreased. 5. Labile hypertension with all its characteristics may or may not coexist with established essential hypertension with all its features. 6. The sympathetic nervous system is also involved in other types of hypertensive disease. Many patients with renovascular hypertension as well as with primary and secondary hyperaldosteronism also have essential hypertension. Angiotensin II affects the sympathetic nervous system and the juxtaglomerular apparatus appears to be beta adrenergic receptor activated, at least in part.

Acetylcholine↗
PubMed1975

[Peripheral secretion and inactivation of catecholamines (adrenaline, noradrenaline, dopamine)].

In spite of the biochemical relationship between catecholamines (E,NE,DA), the unity of the adrenergic system is only apparent; catecholamines are present in numerous pools, which exhibit different anatomical and cellular localizations, secretory patterns, control of release, physiological functions, inactivation schemes and metabolic behaviour. The main sources of catecholamines in the periphery are the orthosympathetic nervous system, which is permanently active in maintaining homoeostasy, and the adrenal medulla, an essential element in the struggle against stress. In addition to these large pools, catecholamines are found also in extra adrenal chromaffin tissue and in sympathetic ganglions; the latter represents a potential store of amines, whilst ganglionic dopamine-rich interneurones are important links in the regulation of orthosympathetic activity. Rather than by a topographic distinction, it seems more satisfactory to classify the catecholamines spread in adrenergic fields into a small number of pools possessing their own physiological functions and inactivation patterns. Two main pools of catecholamines in the periphery may be described: The functional pool, represented by those catecholamines already released, or able to be released; in this pool are found plasma and adrenal medullary catecholamines and NE from sympathetic nerve endings. The tissue pool, consisting of the synthesis and storage compartments, which are poorly penetrated by plasma pool with respect to their high possibilities for synthesis and storage. Catecholamines from cellular bodies and axons of sympathetic neurons and a part of the adrenal medullary amines may be related to it. Two other pools of catecholamines have to be reported: a potential extrachromaffin pool, which is apparently negligible in the physiological state, but able to exhibit its synthetic and secretory capacities in particularly critical situations; an intraganglionic dopamine pool, which plays a modulator role in ganglionic synaptic transmission; its mode of secretion and inactivation are not necessarily the same as those of the above pools. To such a physiological diversity, specific regulatory processes, correspond the aim of which is, to stop physiological activity of released catecholamines, by means of physical and chemical inactivating mechanisms; to limit the amount of released product by local control of the neuromediator outflow; to minimize losses of active compound by neuronal and cellular uptake and perhaps by sulfoconjugation; to destroy the excess of synthesized or reabsorbed amines when tissue or neuronal concentration becomes too high (tissue metabolism).

Acetylcholine↗