Serotonin Cell Research Articles

Constitutive expression of calmodulin-binding phosphoprotein GAP-43 in rat serotonergic and noradrenergic cell groups which project to the spinal cord.

In situ hybridization was combined with serotonin (5-hydroxytryptamine, 5-HT) or tyrosine hydroxylase immunocytochemistry and with Fluoro-Gold retrograde labeling of bulbo-spinal pathways in order to investigate the expression of GAP-43 mRNA in monoamine cell groups of the adult rat brain stem. Consistent with previous reports, GAP-43 mRNA was observed in serotonin and dopamine cell groups in the pons. In addition, GAP-43 expressing cells were observed in all the major monoamine cell groups in the medulla. Thus the B1, B2 and B3 serotonin cell groups all showed high GAP-43 expression in all contained many GAP-43 expressing serotonin cells with spinal cord projections. The A1, A2, A5 and A6 noradrenaline cell groups also showed high GAP-43 expression, although cells with spinal cord projections were largely restricted to the A5 group and A6 subcoeruleus region. In all areas, GAP-43 expressing cells with spinal cord projections were also observed which were not serotonergic or noradrenergic.

Ligand Recognition by the Vesicular Monoamine Transporters

Molecular cloning has identified three distinct proteins responsible for plasma membrane monoamine transport. Although functional analysis indicates that each can recognize multiple monoamines as substrates, selective expression within dopamine, norepinephrine, and serotonin cell populations of the brain suggests that each probably transports a single substrate in vivo . In contrast, molecular cloning has identified two vesicular monoamine transporters (VMATs), one expressed in the adrenal medulla and other neuroendocrine tissues (VMAT1) and the other in the brain (VMAT2). Although VMATs have no sequence similarity to the plasma membrane transporters or receptors for monoamines, they do contain individual residues implicated in substrate recognition by these other proteins. In addition to those residues required for substrate recognition, the comparison of VMAT1 and VMAT2 indicates that other residues may modulate the recognition of ligand. VMAT2 has an apparent affinity for most substrates approximately threefold higher than VMAT1. In addition, only VMAT2 recognizes histamine, and tetrabenazine inhibits only VMAT2. Residues have been identified that have a variety of roles in substrate recognition by VMATs. Analogous to other membrane proteins that interact with monoamines, VMATs contain an aspartate in TMD1 and serines in TMD3 that are required for transport activity.

Pancreatic-duodenal homeobox 1 -role in gastric endocrine patterning

The gastrointestinal tract is subdivided into regions with different roles in digestion and absorption. How this patterning is established is unknown. We now report that the pancreatic-duodenal homeobox 1 gene (pdx1) is also expressed in cells of the distal stomach. Positive cells include subpopulations of the three main endocrine (gastrin, somatostatin and serotonin) cell types of this region. Pdx1 deficient mice were virtually devoid of gastrin cells, had normal numbers of somatostatin cells and increased numbers of serotonin cells. Pdx1 is thus important for development of the gastrin cells of the antropyloric mucosa of the stomach and probably acts by controlling the fate of gastrin/serotonin precursor cells.

Pulmonary neuroendocrine cells in cultures of human infant airway mucosa from postmortem tissues.

Airway mucosa was isolated by enzymatic dissociation from tracheas and bronchi obtained at autopsy from stillbirth, infants, and children. An epithelial cell fraction was recovered that could be cultured on a collagen-coated substratum for at least 7 days. Epithelial cells were identified immunocytochemically with anticytokeratin antibody; pulmonary neuroendocrine cells (PNEC) were identified with antibodies against serotonin, bombesin/GRP, and MOC-1 cell surface antigen. Transmission electron microscopy confirmed neuroendocrine ultrastructural features of PNEC including the presence of neurosecretory dense core vesicles. The ability to recover and maintain viable PNEC in human lung airway epithelial cell cultures from postmortem tissues should facilitate further investigations of PNEC function in normal human lung and in various disease states.

Tetrahydrobiopterin biosynthesis in the rat brain: heterogeneity of GTP cyclohydrolase I mRNA expression in monoamine-containing neurons

GTP cyclohydrolase I is the first and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. A quantitative in situ hybridization technique was used to study the expression of GTP cyclohydrolase I mRNA in the rat brain at the cellular level. Coronal sections between the diencephalon and myelencephalon were exposed to a 35S-labelled antisense GTP cyclohydrolase I cRNA probe. Sections serial to these were hybridized with a 35S-labelled antisense cRNA probe complementary to tyrosine hydroxylase mRNA. Tyrosine hydroxylase and GTP cyclohydrolase I mRNAs were found to colocalize within catecholamine neurons located throughout the brain. The overall distribution of neurons expressing GTP cyclohydrolase I mRNA was observed to correspond exactly to the known distribution of the dopamine, norepinephrine/epinephrine and serotonin-containing cell groups. Overall, a 30-fold range of GTP cyclohydrolase I mRNA expression was observed, with the transcript being significantly more abundant in serotonin than in dopamine or norepinephrine/epinephrine neurons. Comparisons across serotonin cell groups indicated that neurons of the median raphe nucleus, caudal linear nucleus raphe (B8) and the dorsal raphe (B6/B7) expressed the highest levels of GTP cyclohydrolase I mRNA. Comparisons across dopamine cell groups indicated that the transcript was more abundant in neurons of the ventral tegmental area (A10) than in neurons of the substantia nigra pars compacta (A9) and that both A9 and A10 dopamine neurons exhibited higher levels of expression than the DA neurons of the hypothalamus (A11–A14). Norepinephrine neurons of the locus coeruleus (A6) and subcoeruleus (A6v) exhibited significantly higher levels of GTP cyclohydrolase I mRNA than did neurons in other norepinephrine (A1 and A2) or epinephrine (C1 and C2) cell groups. GTP cyclohydrolase I mRNA could not be detected unequivocally in neurons known to contain nitric oxide synthase. Heterogeneity in the level of expression of GTP cyclohydrolase I mRNA by monoamine-containing neurons may play an important role in determining steady state levels of tetrahydrobiopterin and, ultimately, the regulation of monoamine biosynthesis.

Ultrastructural examination of the targets of serotonin-immunoreactive descending interneurons in the guinea pig small intestine.

Serotonin neurons are descending interneurons in the myenteric plexus of the guinea pig small intestine. Preembedding single- and double-label immunocytochemistries at the ultrastructural level were used to identify the targets of these serotonin interneurons. Serial ultrathin sections were taken through a myenteric ganglion that had been processed for serotonin immunocytochemistry. The ganglion contained the cell bodies of 69 neurons, including 2 serotonin neurons and 6 neurons with the ultrastructural features of Dogiel type II cells. For each cell body in the ganglion, the number of serotonin inputs (synapses and close contacts) was determined. About 59% of the cell bodies did not receive any serotonin inputs. The most abundant serotonin terminals were related to two targets: other serotonin descending interneurons and a population of neurons with Dogiel type I morphology, but whose neurochemistry and function is unknown. The serotonin inputs to the serotonin cell bodies were located predominantly on the lamellar dendrites. Each of the Dogiel type II neurons received 3 or fewer serotonin inputs, and none of the serotonin inputs to Dogiel type II neurons formed a synapse. Overall, about 40% of the serotonin inputs formed synapses. The serotonin inputs to neurons that received many serotonin inputs were more likely to show synaptic specializations than serotonin inputs to neurons that received few serotonin inputs. Inhibitory motor neurons contain nitric oxide synthase (NOS). At the light microscope level, serotonin nerve fibers do not form dense pericellular baskets around NOS cell bodies. To determine whether there are serotonin inputs to NOS neurons, serial ultrathin sections were taken through a myenteric ganglion that had been processed for preembedding double-label immunocytochemistry, in which the NOS neurons were labeled with peroxidase-diaminobenzidine and the serotonin neurons with silver-intensified 1 nm gold. Only 1 out of 9 NOS cells examined in serial section received more than 5 serotonin inputs. The results suggest that, in the guinea pig small intestine, the serotonin descending interneurons are not an essential element of the descending inhibitory reflex.

Extent of colocalization of serotonin and GABA in the neurons of the rat raphe nuclei

Previous investigations of the distribution of neurons containing both serotonin and GABA in the brainstem raphe nuclei have yielded discrepant results amongst different authors. This study attempted to clarify the distribution as well as the proportions of raphe and other brainstem neurons that contain both neurotransmitters. All the nine serotonergic cell groups known to be present in the brainstem were examined with an indirect immunofluorescence method using antibodies against serotonin and glutamic acid decarboxylase in colchicine-treated rats. Sections were incubated either simultaneously or sequentially for the two immunolabels. Brainstem neurons that were labelled for both markers were generally infrequent. Of all the serotonin cell groups in the brainstem, the nucleus raphe magnus contained the most double-labelled cells (a mean of 3.6% of a total of 625–1155 serotonin-immunoreactive cells counted in this nucleus), followed by the nucleus raphe obscurus (1.5% of a total of 220–550 serotonin-immunoreactive neurons counted). The dorsal, median and pontine raphe nuclei as well as the supralemniscal nucleus (the B9 group) contained very few double-labelled cells, which comprised a mean of 0.1–0.7% of all serotonin-immunoreactive cells in each of these nuclei. No double labelled cells were present in the caudal linear raphe nucleus or the nucleus raphe pallidus, nor in the B4 group. These results suggest that only a very small percentage of serotonergic neurons in the medullary raphe nuclei (raphe magnus and raphe obscurus) also contain GABA, whereas such cells are virtually absent in the midbrain raphe nuclei or in the non-raphe serotonergic cell groups in the brainstem.

Serotonin uptake inhibitors: uses in clinical therapy and in laboratory research.

Fluoxetine, zimelidine, sertraline, paroxetine, fluvoxamine, indalpine and citalopram are the selective inhibitors of serotonin uptake that have been most widely studied. Some of these compounds are or have been used clinically in the treatment of mental depression, obsessive-compulsive disorder and bulimia, and therapeutic benefit has been claimed in additional diseases as well. By blocking the membrane uptake carrier which transports serotonin from the extracellular space to inside the serotonin nerve terminals, these compounds increase extracellular concentrations of serotonin and amplify signals sent by serotonin neurons. Because serotonin neurons are widespread in the central nervous system, the functional consequences of blocking serotonin uptake are diverse, but are generally subtle. Animals treated with serotonin uptake inhibitors look normal in gross appearance, but effects such as reduced aggressive behavior, decreased food intake and altered food selection, analgesia, anticonvulsant activity, endocrine changes and neurochemical changes have been demonstrated and characterized. Serotonin uptake inhibitors have helped in revealing some dynamics of serotonin neurons; for example, when uptake is inhibited and extracellular serotonin concentration increases, presynaptic as well as postsynaptic receptors for serotonin are activated to a greater degree. A consequence of increased activation of autoreceptors on serotonin cell bodies and nerve terminals is a reduction in firing of serotonin neurons and a decrease in serotonin synthesis and release. The result is a limit on the degree to which extracellular serotonin and serotonergic neurotransmission are increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of familial amyloid associated polyneuropathy on duodenal endocrine cells.

Duodenal endocrine cells in 11 patients with familial amyloid associated polyneuropathy (FAP) were compared with those in 12 healthy volunteers by means of immunohistochemistry and morphometry. The total endocrine cell content, determined by the argyrophilic reaction and chromogranin A immunoreactivity, was significantly reduced in FAP patients compared with controls. There was a significant reduction in the serotonin, cholecystokinin/gastrin, and secretin immunoreactive cell content. A decreased cell content was also noted for somatostatin and gastric inhibitory polypeptide immunoreactive cells but this was not statistically significant. Amyloid deposits were noted in seven of the 11 biopsy specimens from FAP patients, but otherwise the duodenum was histologically normal in both groups. The reduction in endocrine cell content was not correlated with the degree of amyloid deposit in the duodenum. These findings indicate that patients with FAP have reduced intestinal endocrine cells. This does not seem to be related to amyloid deposits in the mucosa or to villous or crypt abnormalities. The observed changes in endocrine cells may contribute to the development of intestinal motility dysfunction and maldigestion in these patients.

Chronic D-fenfluramine decreases serotonin transporter messenger RNA expression in dorsal raphe nucleus

In situ hybridization was used to measure the effects of chronic fenfluramine administration on serotonin transporter messenger RNA expression in cells of the dorsal raphe nucleus complex. Fenfluramine produced a significant, but transient, down-regulation of serotonin transporter mRNA in cells which lie in the ventral portion of the dorsal raphe nucleus, but not in the dorsal part of the dorsal raphe nucleus. Our findings suggest that cells which lie in the ventral part of the dorsal raphe nucleus are more sensitive to the effects of chronic fenfluramine administration, but that fenfluramine does not cause long-term changes in gene expression in serotonin cell bodies.

Differential effects of 5,7-dihydroxytryptamine-induced serotoninergic degeneration on 5-HT 1A receptors and 5-HT uptake sites in the rat brain

The time-course of 5,7-dihydroxytryptamine-induced lesions (2, 5 and 14 days after i.c.v. injection of 150 μg) and the effects of acute reserpine treatment (10 mg/kg, i.p., one or 5 days before scheduled death), were evaluated by autoradiography of [ 3H]paroxetine binding sites in the rat brain. Reserpine had no significant effect on [ 3H]paroxetine binding, indicating that the depletion of serotonin is not sufficient per se to alter the serotonin uptake sites in any region. Two days after the 5,7-dihydroxytryptamine lesion, [ 3H]paroxetine binding was already decreased in the majority of brain regions. In the caudate putamen these binding sites were significantly decreased only 14 days after the lesion, whereas the ventral tegmental area (or the enclosed median forebrain bundle), the dorsal raphe (mainly the ventral portion) and the median raphe maintained their high density of serotonin uptake sites even after 14 days. Results were similar using [ 3H]citalopram as ligand for the serotonin uptake sites, in the brains of rats lesioned 5 days before death; an exception was the ventral portion of the dorsal raphe, where there was a significant increase with [ 3H]paroxetine and a decrease with [ 3H]citalopram binding. In adjacent sections of the same brains we also measured [ 3H]8-OH-DPAT binding, confirming that it completely disappears in the dorsal raphe after the lesion. Thus, considering the extent of serotonin cell body degeneration, there appears to be a paradoxical mismatch between the excessive loss of [ 3H]8-OH-DPAT binding and the resistance of [ 3H]citalopram or [ 3H]paroxetine binding in the dorsal raphe, suggesting that the two binding sites may undergo adaptive regulation in surviving neurons.

Serotonin release and cell proliferation are under the control of α-bungarotoxin-sensitive nicotinic receptors in small-cell lung carcinoma cell lines

Neuronal type nicotinic acetylcholine receptors (nAchRs) have recently been identified in small-cell lung carcinoma. We here show that both nicotine and cytisine stimulate [ 3H]serotonin release in a dose-dependent manner; this effect is antagonized by α-bungarotoxin (αBgtx) and α-conotoxin MI (αCtx). Nicotine and cytisine stimulate in vitro SCLC proliferation and this effect is completely antagonized by both αBgtx and αCtx. By PCR analysis, we demonstrate the presence in SCLC of both the α 7 and the β 2 nAchR subunits mRNA. These data show that nAchRs play an important role in the biology of SCLC, and that αBgtx-sensitive receptors of the α 7 subtype are crucially involved in both the secretagogue and mitogenic effects of nicotinic agonists.

Neuropeptides and monoamines in the carp ( Cyprinus carpio) pretectum: An immunocytochemical study

The distribution of neurotensin, neurokinin A, dynorphin A, galanin, somatostatin-28 (1–12), neuropeptide Y, vasoactive intestinal polypeptide, gastrin-releasing peptide, γ-melanocyte stimulating hormone, α-neo-endorphin, angiotensin H, cholecystokinin-8, serotonin and tyrosine hydroxylase has been studied in the pretectal nuclei of the Cyprinus carpio: nuclei pretectalis superficialis parvicellularis and magnocellularis, pretectalis centralis, pretectalis, and pretectalis periventricularis dorsalis and ventralis using an indirect immunoperoxidase technique. We have found neuropeptide Y and serotonin immunoreactive fibres in all pretectal nuclei, whereas gastrin-releasing peptide immunoreactive fibres were visualized in the nuclei pretectalis superficialis parvicellularis and magnocellularis, pretectalis centralis. pretectalis and pretectalis periventricularis dorsalis; neurokinin A immunoreactive fibres in the nuclei pretectalis superficialis parvicellularis and magnocellularis and pretectalis periventricularis dorsalis; galanin immunoreactive fibres in the nuclei pretectalis superficialis parvicellularis, pretectalis centralis and pretectalis periventricularis dorsalis; and neurotensin immunoreactive fibres in the nucleus pretectalis periventricularis dorsalis. Additionally, immunoreactive cell bodies containing neuropeptide Y were observed in the nuclei pretectalis superficialis parvicellularis and pretectalis periventricularis dorsalis, and serotonin and tyrosine hydroxylase cell bodies were found in the nuclei pretectalis periventricularis dorsalis and ventralis respectively. The presence of the neuroactive substances found in the carp pretectal nuclei suggest that they might be involved in the regulation of certain functions within the visual system.

Measurement of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in cultured rat mesencephalic neurons by high-performance liquid chromatography with electrochemical detection

An HPLC method with electrochemical detection for the simultaneous measurement of serotonin (5-hydroxytryptamine) and 5-hydroxyindoleacetic acid in primary mesencephalic cell culture is described. The serotonin and 5-hydroxyindoleacetic acid cell content was measured on different days of growth in vitro; after twelve days in culture the amounts of serotonin and 5-hydroxyindoleacetic acid detected were 916.0 ± 70.2 and 215.8 ± 15.5 pg per well, respectively. The heterogeneity of neurons in our cultures and their capacity to take up serotonin were assessed by measuring the amounts of exogenous serotonin taken up in the presence of different monoamine uptake inhibitors. This method, sensitive and reliable, can represent a valid alternative to the use of labelled compounds.

Pineal serotonin is resistant to depletion by serotonergic neurotoxins in rats

Administration of 3,4-methylenedioxymethamphetamine (MDMA) or para-chloroamphetamine (pCA) to adult rats is neurotoxic to serotonin (5HT) nerve terminals and cell bodies. MDMA (10 mg/kg) reduces 5HT levels in the frontal cortex, medial basal hypothalamus, and striatum acutely and 17 days after a series of multiple injections. The acute reductions occur within 1-2 hr after injection of doses greater than 3 mg/kg. A single injection of pCA reduces 5HT levels in the above mentioned brain regions as well as in the brain stem. However, none of these treatments are able to alter 5HT levels in the pineal gland. It appears that the pineal does not contain the 5HT reuptake system that is thought to be necessary for the neurotoxicity of MDMA and pCA.

Distribution of the pro-opiomelanocortin-immunoreactive axons in relation to the serotoninergic neurons in the dorsal raphe nucleus of the rat.

The anatomical relationships between pro-opiomelanocortin-containing axons and serotonin neurons in the nucleus raphe dorsalis (NRD) of the rat were examined at the light microscope level with antibodies against CLIP (corticotropin-like intermediate lobe peptide), alpha-MSH (alpha-melanocyte-stimulating hormone) and serotonin. Sequential double labeling was performed with either immunofluorescence or peroxidase-antiperoxidase techniques. It was observed that the network of POMC-immunoreactive axons displayed a gradient of decreasing density from rostral to caudal levels and from dorsal to ventral parts or the NRD. The examples of close proximity between immunoreactive axons and serotonin cell bodies or dendrites were rather scarce. On the whole, the immunoreactive fibers seemed to run quasi-independently of the serotonin neurons.

Topographical organization in the origin of serotoninergic projections to different regions of the cat cerebellar cortex

The distribution of serotonin immunoreactivity in the cat cerebellum was studied by using the indirect antibody peroxidase-antiperoxidase (PAP) technique. Furthermore, the origin of these chemically defined afferents was determined by combining the retrograde transport of horseradish peroxidase (HRP) with the PAP technique. In the cerebellar cortex, serotonin immunoreactivity is present in a plexus of beaded fibers that is confined almost exclusively to the granule and Purkinje cell layers; a few fibers are present in the molecular layer. Serotoninergic axons and varicosities have a dense and uniform distribution throughout all lobules of the cerebellum with the exception of lobule X where the fiber density is sparse. Serotonin cell bodies were not found within the cerebellar cortex. However, following pretreatment with pargyline and L-tryptophan, serotonin positive cell bodies were found in all deep cerebellar nuclei as well as the raphe and reticular nuclei in the brainstem. The present study demonstrates that the serotoninergic projection to the cat's cerebellum has some degree of topographical organization. Serotoninergic fibers in the anterior vermis (lobules I-V) were shown to arise from neurons located within the paramedian reticular nucleus, the lateral reticular nucleus, and the lateral tegmental field. Injections of HRP into either the posterior vermis (lobule VI-IX) or the paramedian lobule, labeled serotoninergic neurons exclusively in the lateral reticular nucleus. Lobus simplex, crus I and crus II (the hemisphere) receive a serotoninergic input from cells located in the lateral tegmental field, the peri-olivary reticular formation and the paramedian reticular nucleus. In no cases were neurons in the raphe double-labeled, although there were cells positive for HRP or serotonin alone. The data indicate that there is a topographical organization in the serotoninergic projection from the caudal brainstem to specific regions of the cat's cerebellar cortex. In addition to climbing and mossy fibers, this projection represents a third major source of cerebellar afferents based on its dense and widespread distribution as well as its morphological and chemical characteristics.

Intra-midbrain raphe injections of the neurokinin-3 agonist senktide inhibit food and water intake in the rat

Microinjection and lesion studies have implicated the midbrain dorsal (DR) and median raphe (MR) nuclei in behavioral arousal. This behavioral state is manifested as locomotor hyperactivity, hyperphagia, hyperdipsia and increases in plasma corticosteroid release. Intra-midbrain raphe injections of the GABA A agonist muscimol elicit this behavioral activation. We have demonstrated that similar infusions of tachykinins produce locomotor hyperactivity through activation of neurokinin-3 (NK-3) receptors located on serotonin cell bodies. The purpose of the present study was to determine the effects of intra-MR and DR infusions of senktide, an NK-3 agonist, on food and water consumption in nondeprived rats. Male Sprague-Dawley rats were implanted with indwelling intra-MR or intra-DR cannula. Infusions of muscimol (25 ng/0.5 μl) into the MR increased water intake, while MR and DR infusions increased food consumption. In contrast, intra-MR injections of senktide decreased water intake and intra-MR and DR injections decreased food intake. The results suggest that the behavioral states induced by muscimol and neurokinin infusions into the raphe are distinct and that raphe/neurokinin pathways are involved in consummatory mechanisms.

Serotonin release in lateral and medial hypothalamus during feeding and its anticipation

In the present experiments we extend previous findings that established a relationship between feeding behavior and hypothalamic serotonin as measured by in vivo microdialysis. The new result is hypothalamic release of serotonin in anticipation of eating when the animal sees and smells food. We have now verified brain serotonin peaks in four different ways: 1. 1) a serotonergic reuptake blocker (fluoxetine 1 or 10 μM) in the perfusion medium raised basal levels of serotonin. 2. 2) every sample was oxidized at two potentials using a dual potentiostat to confirm the voltage characteristics of each peak. 3. 3) serotonin peaks were reduced by the selective serotonin cell body agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), thus helping confirm that most of the serotonin observed in these experiments was neuronal in origin, and 4) lateral and medial hypothalamic microdialysis probes were used simultaneously to monitor the degree of diffusion from one to the other. The results show that extracellular serotonin increases at both sites during preingestive events as well as during eating, but not afterwards.

Innervation of the serotonin‐immunoreactive cells distributed in the wall of the common carotid artery and its branches in the chicken

In the chicken, serotonin-immunoreactive cells were widely distributed not only in the carotid body but also in the wall of the common carotid artery and around each artery arising from the common carotid artery. Almost all of the serotonin cells in the wall of the common carotid artery were intensely immunoreactive to the neuropeptide Y, met- and leu-enkephalin antisera, whereas in the carotid body only a few cells were immunoreactive to these antisera. Innervation of the serotonin cells in and around arteries of chickens was investigated by immunohistochemistry and electron microscopy, in comparison with that of the carotid body. The serotonin cell groups in and around arteries, as well as the carotid body, received numerous peptidergic nerve fibers. Calcitonin gene-related peptide (CGRP)- and substance P-immunoreactive varicose nerve fibers were densely distributed, and somatostatin-immunoreactive fibers were moderately distributed in the serotonin cell groups. Galanin- and vasoactive intestinal peptide (VIP)-immunoreactive fibers were sparsely distributed in the cell groups. By electron microscopy, the serotonin cells in and around arteries were characterized by the presence of numerous dense-cored vesicles, 70-220 nm in diameter. The granule-containing cells were in close association with numerous axons. Naked axons regarded axon terminals were frequently apposed on the granular cells. The axon terminals were usually long and often partly invested the granular cells. Numerous synaptic junctions were detected along the contact between the granular cells and axon terminals. Most of the synaptic junctions showed afferent morphology; the secretory granules were accumulated near and attached to the asymmetrical membrane thickenings. Thus, the serotonin cells in and around arteries, like the carotid body, constitute chemoreceptive tissue.