Mechanism of age-dependent involution in embryonic chick notochords

To study the possible mechanism of the age-dependent involution of the notochord, isolated mesenchymefree notochords of chick embryos were cultured in vitro and compared with their counterparts in vivo. Two different aspects were evaluated: (1) DNA synthesis measured by [³H]thymidine incorporation and visualized by autoradiography and (2) cell death quantified by counting the number of pyknotic nuclei. The results demonstrate that [³H]thymidine uptake by notochords shows an age-dependent decrease in vitro as well as in vivo. The number of [³H]thymidine-labelled notochord cells, however, is higher in vitro than in vivo. At the same time, there is an age-dependent increase in pyknosis in the notochord in vivo and in vitro. So, during the aging process, the number of both pyknotic nuclei and of [³H]thymidine-labelled nuclei suggest a high turnover of notochord cells in vitro. From these results, we can conclude that the process of involution in aging notochord seems to be controlled by a programmed intrinsic process, which might be influenced partially by the microenvironment in vivo.     

Attraction of primordial germ cells by notochord in seven somites chick embryo

Summary Chemical studies in chick embryo have indicated the existence of proteoglycan in notochordal sheath. Primordial germ cells were observed with scanning electron microscope on the notochord dorsal face, surrounded with perichordal material. We postulate the identification of such a material with proteoglycan which could attract primordial germ cells to the notochord.     

Existence of cholinergic receptors in the very young chick embryo]

The injection of certain cholinergic agents in the yolk sac of young Chick embryos (40 to 48 hrs. of incubation) gives rise to a twisting of the cervical notochord and spinal cord and contraction of the cervical somites. These morphogenetic changes result in spinal column malformations in older embryos. The effects of the cholinergic agents are inhibited by simultaneous treatments with a cholinergic agonist and an antagonist or a cholinergic receptor ligand. The results lead to the assumption that the early embryos already possess cholinergic receptors, probably located in the notochord.     

Histochemical localization of lactate dehydrogenase in the trout embryo (Salmo irideus, Gibb) during early organogenesis of the cord and the neural tube]

The histochemical study of the LDH in the Trout embryo during the early organogenesis shows a specific localization in notochord cells, in mesodermic cells of the terminal knob and in some prosencephalic neuroblasts. The role of the LDH in the metabolism of NAD as well as in the energetic metabolism of embryonic cells is discussed.     

Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new perspectives

Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis. Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut may open new therapeutic strategies in hepato-gastrointestinal diseases. Received 15 August 2007; received after revision 1 November 2007; accepted 5 November 2007     

Circulating serotonin in vertebrates

The role of circulating serotonin is unclear and whether or not serotonin is present in the blood of non-mammalian species is not known. This study provides the first evidence for the presence of serotonin in thrombocytes of birds and three reptilian species, the endothermic leatherback sea turtle, the green sea turtle and the partially endothermic American alligator. Thrombocytes from a fresh water turtle, American bullfrog, Yellowfin tuna, and Chinook salmon did not contain serotonin. Serotonin is a vasoactive substance that regulates skin blood flow, a major mechanism for endothermic body temperature regulation, which could explain why circulating serotonin is present in warm-blooded species. The temperature sensitivity of human blood platelets with concomitant changes in serotonin content further supports a link between circulating serotonin and thermoregulation. Phylogenetic comparison of the presence of circulating serotonin indicated an evolutionary divergence within reptilian species that might coincide with the emergence of endothermy.Received 2 April 2005; received after revision 15 May 2005; accepted 15 June 2005     

Morphological effects of serotonin and ketanserin on embryonic chick skin in vitro

Cell and organotypical cultures are used to study the direct effect of serotonin and of ketanserin, a serotonin antagonist, on dermal and epidermal cells of embryonic chick skin. Ketanserin stimulates the increase in cell number and inhibits the differentiation, whereas serotonin stimulates differentiation and inhibits the increase in cell number.     

Morphological effects of serotonin and ketanserin on embryonic chick skin in vitro

Summary Cell and organotypical cultures are used to study the direct effect of serotonin and of ketanserin, a serotonin antagonist, on dermal and epidermal cells of embryonic chick skin. Ketanserin stimulates the increase in cell number and inhibits the differentiation, whereas serotonin stimulates differentiation and inhibits the increase in cell number.     

Presence in and effects of pineal indoleamines at very low level of phylogeny

The unicellular organism Tetrahymena contains serotonin and is able to take up the hormone from its mileiu. The serotonin content of the cell changes as a function of the presence of foreign exogenous hormones. This indicates a possible role of serotonin as a chemical mediator. Exogenous serotonin stimulates the RNA synthesis of Tetrahymena, and it was the only one among the hormones studied which kept the RNA level durably high. Serotonin stimulates phagocytosis and growth of Tetrahymena, and its precursors also stimulate growth. Serotonin can imprint Tetrahymena, and as a consequence of this the effect of the hormone increases in the case of further encounters. Treatment with serotonin-related molecules soon after imprinting can reduce the effect of imprinting. Melatonin can contract the pigment cells of Planaria; however, its precursors serotonin and tryptamine can do this more intensely. Both melatonin and serotonin can influenc the regeneration of Planaria, with effects which differ when different phenomena are studied. Evolutionary theories are discussed.     

Ovarian serotonin content in relation to ovulation

Summary In the mature cyclic female rat, analysis for ovarian serotonin content reveals comparatively high serotonin content. Fluctuation of serotonin content was observed; peak for serotonin was observed at estrus. In gonadotropintreated immature rats, there was no detected ovarian serotonin using this procedure. It was concluded that ovaries from gonadotropin-treated immature rats are physiologically different from ovaries taken from mature cyclic rats.Supported by NIH Grant RR8111.National Institutes of Health, MBS Trainee.     

Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: a possible new mechanism for hypoxia-induced vasodilatation of the rat heart

In this report we demonstrate the immunocytochemical localization of serotonin in endothelial cells of rat coronary vessels and a significant increase in the release of serotonin into the perfusate of Langendorff rat heart preparations during hypoxia. It is suggested that serotonin, localized in endothelial cells, is released during hypoxia and could provide part of a pathophysiological mechanism for vasodilatation to protect the heart from damage due to hypoxia.     

Corticosteroidogenesis by isolated human adrenal cells: effect of serotonin and serotonin antagonists.

The direct effect of serotonin and antiserotonin agents on adrenal steroid biosynthesis was studied in isolated adrenal cells derived from patients with Cushing's syndrome. The results indicate that serotonin increases corticosterone production, while the serotonin antagonists cyproheptadine and methysergide depress adrenal steroid - particularly cortisol and aldosterone - biosynthesis.     

Comparative study of the sensitivity of acetylcholinesterases and cholinesterases from animal and bacterial sources to inhibition by serotonin and its derivatives.

Serotonin was found to inhibit human erythrocyte and electric-eel acetylcholinesterase activities. The serotonin amino group, free of negative charges in its vicinity and its hydroxyl group, were important for the inhibition. Serotonin precursors and several related compounds had little or no effect. Human plasma cholinesterase was also inhibited by serotonin and tryptamine. In contrast to these animal enzymes, the cholinesterase of Pseudomonas aeruginosa was refractory to serotonin and its derivatives under the same experimental conditions.     

Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: A possible new mechanism for hypoxia-induced vasodilatation of the rat heart

Summary In this report we demonstrate the immunocytochemical localization of serotonin in endothelial cells of rat coronary vessels and a significant increase in the release of serotonin into the perfusate of Langendorff rat heart preparations during hypoxia. It is suggested that serotonin, localized in endothelial cells, is released during hypoxia and could provide part of a pathophysiological mechanism for vasodilatation to protect the heart from damage due to hypoxia.This research was supported by the British Heart Foundation and the excellent technical assistance of Jon Bokor is gratefully acknowledged.     

Comparative study of the sensitivity of acetylcholinesterases and cholinesterases from animal and bacterial sources to inhibition by serotonin and its derivatives

Summary Serotonin was found to inhibit human erythrocyte and electric-eel acetylcholinesterase activities. The serotonin amino group, free of negative charges in its vicinity and its hydroxyl group, were important for the inhibition. Serotonin precursors and several related compounds had little or no effect. Human plasma cholinesterase was also inhibited by serotonin and tryptamine. In contrast to these animal enzymes, the cholinesterase ofPseudomonas aeruginosa was refractory to serotonin and its derivatives under the same experimental conditions.     

Effects of captivity on glucose tolerance in dogs

Captivity decreased tolerance to glucose and increased blood serotonin levels in 6 normal dogs investigated. Return to freedom brought normalization in the glucose tolerance test and reverted blood serotonin to control levels.     

Possible involvement of indolamines in the glycogenic effect of the convulsant methionine sulfoximine in rat brain.

The aim of the present investigation was to look for the mechanisms causing disturbances in carbohydrate metabolism during the action of the epileptogenic agent methionine sulfoximine. The levels of glucose, glycogen, and indolamines were measured in seven different regions of rat brain. Methionine sulfoximine induced a decrease in serotonin level which was roughly dose-dependent. There were no obvious changes in tryptophan and 5-hydroxyindoleacetic levels in any area. Methionine sulfoximine induced the known increase in glucose and glycogen levels. The direct precursor of serotonin. 5-hydroxytryptophan, and benserazide (a decarboxylase inhibitor) were then injected into rats in association with methionine sulfoximine. In this case, methionine sulfoximine failed to induce seizures. Moreover, the serotonin level was unchanged and the carbohydrate content did not significantly increase. There was only a rise in 5-hydroxyindoleacetic acid level. This work shows a striking parallelism between serotonin decrease and glycogen increase.     

Possible involvement of indolamines in the glycogenic effect of the convulsant methionine sulfoximine in rat brain

Summary The aim of the present investigation was to look for the mechanisms causing disturbances in carbohydrate metabolism during the action of the epileptogenic agent methionine sulfoximine The levels of glucose, glycogen, and indolamines were measured in seven different regions of rat brain. Methionine sulfoximine induced a decrease in serotonin level which was roughly dose-dependent. There were no obvious, changes in tryptophan and 5-hydroxyindoleacetic levels in any area. Methionine sulfoximine induced the known increase in glucose and glycogen levels. The direct precursor of serotonin, 5-hydroxytryptophan, and benserazide (a decarboxylase inhibitor) were then injected into rats in association with methionine sulfoximine. In this case, methionine sulfoximine failed to induce seizures. Moreover, the serotonin level was unchanged and the carbohydrate content did not significantly increase. There was only a rise in 5-hydroxyindoleacetic acid level. This work shows a striking parallelism between serotonin decrease and glycogen increase.     

Hypnotic effect of serotonin administered in the vago-aortic afferent pathway

A minute amount of serotonin injected in the nodose ganglion circulation area develops abrupt myosis and general electrocortical synchronization activity in "encéphale isolé" Cat preparation. This hypnogenic effect of serotonin can still be reproduced after transection of vago-aortic nerves caudally to the nodose ganglia. The same injections become ineffective after rostral transection of the same pathway. These results suggest that serotonin may trigger some signs of sleep through peripheric nervous elements in which are probably localized in the nodose ganglia.     

Corticosteroidogenesis by isolated human adrenal cells: Effect of serotonin and serotonin antagonists

Summary The direct effect of serotonin and antiserotonin agents on adrenal steroid biosynthesis was studied in isolated adrenal cells derived from patients with Cushing's syndrome. The results indicate that serotonin increases corticosterone production, while the serotonin antagonists cyproheptadine and methysergide depress adrenal steroid-particularly cortisol and aldosterone-biosynthesis.The authors are indebted to Dr. M. Kárteszi, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, for the determination of plasma ACTH by radioimmunoassay in our patients, and to Prof. P. Vecsei, Department of Pharmacology, University of Heidelberg, providing us with highly specific antisera for corticosteroids RIA-s.