Gene/Protein Disease Symptom Drug Enzyme Compound
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A highly specific serotonin binding protein (SBP) has been found in serotonergic neurons in both brain and gut. This protein has an extremely high affinity for serotonin and may be a storage protein. Serotonin is found in many endocrine cells, including parafollicular cells of the sheep thyroid, as well as in neurons. SBP is also present in sheep thyroid. The present study was done to localize the protein in the gland. Thyroid glands were divided into five segments. Concentrations of serotonin and SBP, as well as parafollicular cell volume were measured in each. Serotonin was assayed by enzymatic conversion to melatonin using tritiated S-adenosylmethionine. SBP was assayed by molecular sieve chromatography on sephadex G-50. The relative volume of parafollicular cells was obtained by stereological analysis of electron micrographs. Experiments were also done to demonstrate these cells by histofluorescence and radioautography following incubation with tritiated 5-hydroxytryptophan. Good correlations were found between serotonin and SBP concentrations, and parafollicular cell volume. These peaked in the rostro-central portion of the gland and were minimal at the poles. We conclude that thyroid SBP is probably localized in parafollicular cells.
Anat Rec 1979 Feb
PMID:Localization of a highly specific neuronal protein, serotonin binding protein, in thyroid parafollicular cells. 42 98

The neuroepithelial cells (NECs) of the fish gill filament share several morphofunctional features with the cells of the neuroepithelial bodies in the lungs of air-breathing vertebrates. In the present study, a detailed indolamine-immunocytochemical analysis of the branchial neuroepithelial cells and nerves was undertaken in non-teleost and teleost species, with particular emphasis on the latter. In the rainbow trout, Oncorhynchus mykiss, the chemical degeneration of either catecholaminergic (by 5- and 6-hydroxydopamines) or indolaminergic (by 5,6-dihydroxy-tryptamine) innervations associated with the NECs was studied using electron microscopy. In teleosts, the NECs are located primarily on the distal half of the filament. In the trout particularly, these cells are innervated mainly by non-indolaminergic nerves taking up sympathetic neurotoxins. The proximal half of the filament contains isolated NECs innervated additionally by intrinsic indolaminergic neurons. Serotonin-like immunoreactivity of the NECs is evident in the granular vesicles packed within the basal soma and processes which surround non-vascular and vascular smooth muscles in the filament. Apical processes from the neuroepithelial cells occasionally contact the water on the surface of the filament epithelium. The secretory function of the NECs is discussed with reference to the probable involvement of serotonin in the modulation of fish gill function. In addition, their connections with both central and branchial nervous systems suggest a possible chemoreceptor role.
Anat Rec 1992 May
PMID:The neuroepithelial cells of the fish gill filament: indolamine-immunocytochemistry and innervation. 160 74

The presence of serotonin in the Merkel cells of pig snout epidermis was investigated by the peroxidase-antiperoxidase immunohistochemical technique. Serotonin-like immunoreactive Merkel cells were found in groups located at the base of epidermal rete pegs and in the external root sheath of sinus hair follicles (vibrissae). Immunoreactivity was stronger on the basal side of the Merkel cells, where dense-cored granules are most numerous. Neither the nerve terminal associated with the Merkel cell nor the neighbouring epidermal cells were immunostained. These results are the first evidence of serotonin-like immunoreactivity in mammalian Merkel cells. The fact that immunoreactivity is strongest in those parts of the Merkel cells with the highest granule density suggests that in these cells serotonin is probably localized in the dense-cored granules.
Anat Rec 1989 Dec
PMID:Localization of serotonin-like immunoreactivity in the Merkel cells of pig snout skin. 258 41

The hypothesis that the secretory granules of mammalian gonadotrophs are heterogeneous was tested. Previous studies had shown that all of the granules contain beta-luteinizing hormone (beta-LH) immunoreactivity, and some contain beta-follicle stimulating hormone (beta-FSH) or 5-HT immunoreactivity. Moreover, differential release of beta-LH and beta-FSH has also been demonstrated. In the current study the pituitary glands of mice were investigated immunocytochemically at the ultrastructural level with antisera directed against human growth hormone (GH), beta-LH, beta-FSH, and 5-HT. The immunoreactivities of beta-LH, beta-FSH, and 5-HT were restricted to gonadotrophs. No 5-HT immunoreactivity was seen in somatotrophs, identified by the immunoreactivity of GH in the secretory granules of these cells. Antisera to beta-LH labeled all gonadotroph granules; however, anti-beta-FSH and anti-5-HT sera labeled only subsets of the granules. The proportion of granules labeled could not be increased by doubling the concentration of anti-beta-FSH serum. The incidence of double labeling of granules by antisera to beta-FSH and 5-HT was significantly less than that predicted from the incidence of granule labeling by either reagent alone. It is concluded that beta-FSH and 5-HT immunoreactivities do not co-exist in the same secretory granules of gonadotrophs; therefore, these granules are heterogeneous and there must be at least two types of granules. It is possible that the two types of granules may be responsive to different second messengers, thereby explaining the differential release of LH and FSH.
Anat Rec 1987 Dec
PMID:Two types of secretory granules in gonadotrophs: discrimination by the simultaneous EM immunocytochemical localization of serotonin and beta-follicle stimulating hormone. 312 65

The paper reports on the pharmacological properties of N-[beta-[4-(beta-phenylethyl)phenyl]-beta-hydroxyethyl]imidazole hydrochloride (denzimol, Rec 15-1533), a compound endowed with anticonvulsant properties, and its possible side effects. Effects on the CNS, effects on vigilance and general motility are similar to those of phenytoin and occur at doses much above anticonvulsant levels. The drug has good in vitro antihistamine, anticholinergic and anti-5-HT activity which accounts for the effects on the gastrointestinal system e.g. inhibition of gastric secretion and motility and anti-ulcer properties. There was no significant effect on the cardiovascular system or respiration, except an interesting antiarrhythmic activity.
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PMID:Denzimol, a new anticonvulsant drug. II. General pharmacological activities. 668 94

Pulmonary neuroendocrine cells (PNEC) are numerous in the fetus where they have been implicated to have a role in fetal lung development. We assessed the effects of putative growth factors, gastrin releasing peptide (GRP), cholecystokinin (CCK), gastrin (GN), serotonin (5-HT), and epidermal growth factor (EGF), some of which are produced by PNEC, either alone or in combination, on cultured fetal rabbit PNEC from 20, 24, and 28 day fetuses. GRP increased the total protein of the cultures over a 7 day period in an age-dependent manner, with greatest effect in cultures from the 24 day fetus, no effect with the 28 day fetus, and an inhibitory effect on 20 day cultures. This was accompanied by an increase in PNEC, which could be blocked by treatment of the cultures with a monoclonal antibody to GRP (2A11). There was no increase in 3H-thymidine labeling of PNEC in GRP treated cultures but an increase in numbers of cells partially stained for 5-HT, suggesting the induction of a precursor cell. Other growth factors had neither an inhibitory nor a stimulatory effect either alone or in combination with GRP. Preliminary studies with 125I-GRP receptor localization suggests that the GRP receptor is mostly expressed on pulmonary fibroblasts, and less on epithelial cells, so that the role for GRP in fetal lung development, at least in the rabbit, is probably indirect, acting via a paracrine mechanism.
Anat Rec 1993 May
PMID:Paracrine effects of bombesin/gastrin-releasing peptide and other growth factors on pulmonary neuroendocrine cells in vitro. 838 33

Pulmonary neuroendocrine (NE) cells including the innervated clusters of NE cells--neuroepithelial bodies (NEB)--are difficult to study because of their small numbers and diffuse distribution within the airway mucosa of the lung. We have previously reported a method for isolation and culture of NE cells from rabbit fetal using a combination of mechanical and enzymatic dissociation followed by gradient centrifugation. This method provides single cell suspension of mixed lung cells enriched in NE cells, particularly those originating from NEB. This study further validates our in vitro model by detailed morphologic characterization of cultured NEB cells using high resolution light microscopy, transmission and scanning electron microscopy, HPLC for detection of serotonin (5-HT), and molecular (Northern blot) analysis of mRNA encoding for 5-HT synthesizing enzymes, tryptophane hydroxylase, and aromatic L-amino acid decarboxylase. In addition the effects of hypoxia on NEB cells in vitro were investigated to define the role of these cells as possible airway chemoreceptors. Exposure of NEB cultures to hypoxia resulted in decreased intracellular content of 5-HT accompanied by increased exocytosis of dense core vesicles (DCV). The amount of 5-HT release correlated with the degree of hypoxia, suggesting modulation by ambient pO2 levels. The role of Ca2+ ions in exocytosis of DCV and 5-HT release from NEB cells was tested in experiments with Ca2+ ionophore (A23187). Exposure of cultures to 5 micrograms/ml of ionophore resulted in up to 40% reduction in 5-HT content of NEB cultures as well as increased exocytosis of DCV. Our overall findings are consistent with a view that NEB cells are chemosensory in nature and that Ca2+ signaling pathway is involved in stimulus-secretion coupling. Further refinements in cell separation and culture methodology are required before more detailed investigation of NEB cell membrane properties, signal transduction mechanisms, and intracellular signaling pathways can be carried out.
Anat Rec 1993 May
PMID:Cell biology of pulmonary neuroepithelial bodies--validation of an in vitro model. I. Effects of hypoxia and Ca2+ ionophore on serotonin content and exocytosis of dense core vesicles. 850 15

Recently it has been observed that a subpopulation of gut endocrine cells in vertebrates express Trk-like proteins, suggesting that neurotrophins could regulate the synthesis and storage of amines and peptides of these cells. Nevertheless, the peptides and amines present in the endocrine cells that express Trks have not been characterized. In this study we used immunohistochemistry to investigate the occurrence of Trk-like proteins (TrkA-like, TrkB-like and TrkC-like) and the possible co-localization of these with peptides and/or biogenic amines in the endocrine cells of the stomach of three teleost (bass, gilt-head and scorpionfish). No TrkA-like immunoreactivity (IR) was detected in the stomach of these species, whereas TrkB-like IR and TrkC-like IR were observed in numerous cells of the gastric epithelium. TrkB-like immunoreactive cells were present in all three species examined, and were particularly abundant in the blind sac. Conversely, TrkC-like immunoreactive cells were found only in the bass stomach, apparently co-localized with TrkB-like IR. TrkB-like IR was found co-localized with somatostatin IR in scorpionfish, and with somatostatin and CGRP IR in gilt-head and bass. Gastric endocrine cells expressing 5-HT, glucagon, insulin, met-, leu-enkephalin, substance P, PYY, VIP, CCK, NPY, bombesin and motilin were unreactive for Trk-like proteins. The present results provide direct evidence for the occurrence of Trk-like neurotrophin receptor proteins in a subpopulation of the teleostean gastric endocrine cells and suggest that neurotrophins could regulate, as in neurons, the expression of some neuropeptides such as somatostatin and CGRP.
Anat Rec 1999 11 01
PMID:Co-localization of Trk neurotrophin receptors and regulatory peptides in the endocrine cells of the teleostean stomach. 1052 80

This report summarises the characteristics of target specific projection and neurochemical coding patterns of motor and interneuronal pathways in the gastric enteric nervous system (ENS) which are involved in the innervation of the mucosa, the circular and the longitudinal muscle. The pathways were identified by retrograde tracing and further characterised by optical and intracellular recordings of the synaptic activation of muscle motor neurones, and by recordings of pathway-specific muscle responses. All motor pathways had polarised projections consisting of ascending cholinergic and descending nitrergic populations. Thus, both muscle layers were innervated by excitatory and inhibitory motor neurones. Their projections indicated the presence of intrinsic circuits that mediate excitatory and inhibitory components of a peristaltic reflex and/or are involved in reflex mediated changes in gastric tone. Although polarised projections were also identified for interneuronal pathways, a substantial proportion of descending interneurones was cholinergic. Interneurones and longitudinal muscle motor pathways had longitudinal projection preferences whereas circular muscle motor pathways had circumferential projection preferences. Target-specific coding was primarily revealed for cholinergic populations; ChAT/ENK/+/-SP neurones projected to the muscle layers, ChAT/NPY/+/-VIP projected to the mucosa and ChAT/+/-SP/+/-5-HT/+/-Calret/+/-Calb were interneurones. Muscle strip recordings revealed the functional significance of ascending excitatory and descending inhibitory pathways to the circular muscle and the prominent influence of ascending and descending cholinergic interneurones which activated excitatory and inhibitory circular muscle motor neurones through nicotinic synapses. It is concluded that enteric pathways in the stomach have region specific features which reflect structural and functional adaptation of the gastric ENS.
Anat Rec 2001 01 01
PMID:Enteric pathways in the stomach. 1114 28

Pulmonary neuroendocrine cells (PNECs) have been implicated in the development of small cell lung carcinoma (SCLC) and pediatric asthma, and smoking is a risk factor for both diseases. We as well as others have shown that the alpha(7) nicotinic acetylcholine receptor (alpha(7) nAChR) regulates the release of 5-hydroxytryptamine (5-HT, serotonin) in PNECs and SCLC. Serotonin is an autocrine growth factor for PNECs and SCLC and acts as broncho-constrictor. We found that nicotine and its nitrosated carcinogenic derivative 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) bind to the alpha(7) nAChR in SCLC and PNECs, resulting in the influx of Ca(2+), release of 5-HT, and activation of a mitogenic pathway mediated by protein kinase C (PKC), Raf-1, mitogen activated protein kinase (MAPK) and c-myc. Exposure to 10% CO(2) acted synergistically. Unstimulated SCLC cells from smokers demonstrated high base levels of 5-HT release and of individual downstream signaling components in comparison to PNECs. Subchronic exposure of PNECs to NNK up-regulated the alpha(7) nAChR and its associated serotonergic mitogenic pathway in PNECs, an effect that may contribute to the development of SCLC in smokers and pediatric asthma in children of mothers who smoke.
Anat Rec A Discov Mol Cell Evol Biol 2003 Jan
PMID:Receptor-mediated effects of nicotine and its nitrosated derivative NNK on pulmonary neuroendocrine cells. 1249 89


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