Peptidergic Nerve Research Articles

Evolving the concept of regulation of vascular tone in humans

Elucidation of mechanisms regulating microcirculatory vascular tone is a key issue in the knowledge of human pathophysiology. Anandamide is an endogenous lipidic cannabinoid (CB) characterized by potent vasodilator activity acting mainly through the activation of CB receptors, located on the vessel walls, and the vanilloid receptor 1, located on sensory peptidergic nerve endings within the external layers of vessel walls. In humans, cutaneous anandamide administration causes forearm skin vasodilation by activating vanilloid receptor 1 presumably on primary sensory nerves, while intrabrachial infusion of the same compound is devoid of effect on forearm muscle microcirculation. Taken together, these results indicate that, apart from a possible distrectual difference, the effect of anandamide is specific for the abluminal, but not for the endoluminal, part of the vessel wall. Thus, it is conceivable that, at least in the peripheral microcirculation, this compound could act as an autocrine/paracrine agent and not as a circulating hormone. In line with this possibility, it has been demonstrated that anandamide can be produced by macrophages and therefore its biological effect might increase in clinical conditions characterized by augmented activity of this cell line, including cardiogenic, hemorrhagic and endotoxic shock and even in atherosclerosis, inflammation and ischemia. Moreover, increased serum values of anandamide have been found in patients with endotoxic shock. However, decisive information concerning the role of anandamide in humans will be obtained when specific antagonists or inhibitors will be available. In that case, the anandamide system might represent a potential target for the treatment of important cardiovascular conditions, including severe shock.

Expression of neurotransmitters and neurotrophins in human adenoid tissue

Mucosae-associated lymphoid tissues are richly innervated and the mucosae contain peptidergic nerve endings associated with different types of cells and macrophages. The lymphatic tissue is known to interact with the nervous system and several organs, implicated in the host response to a wide range of stressors, and is also richly innervated. We focussed our attention on the immune organs with particular regard to the human adenoid lymphatic tissues in order to investigate the neuroimmune links and the possible existence of relationships among different neurotransmitters and lymphocytes, macrophages, epithelial cells and nerve fibers by testing the expression of certain neurotransmitters and neurotrophins (NTs) with their own receptors.

Neural surveillance of skeletal homeostasis

Endowed with sympathetic and peptidergic nerves, the vertebrate skeleton is under constant surveillance by the nervous system. In addition to pituitary hormone secretion, centrally regulated sympathetic release, as elegantly demonstrated by Karsenty and colleagues, integrate to control both components of skeletal remodeling, osteoblastic bone formation, and osteoclastic bone resorption (Elefteriou et al., 2005).

Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin

Cannabinoid receptors mediate the psychopharmacological action of marijuana and have been localized in the central and peripheral nervous system as well as on cells of the immune system. Up to now, two cannabinoid receptors (CB1 and CB2) have been cloned and recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in the skin. In the present immunohistochemical investigation we determined the precise localization of CB1 and CB2 in sections of human skin and in one case of mastocytosis. CB1 and CB2 immunoreactivity was observed in cutaneous nerve fiber bundles, mast cells, macrophages, epidermal keratinocytes, and the epithelial cells of hair follicles, sebocytes and eccrine sweat glands. In epidermal keratinocytes, hair follicle and sebaceous glands, CB1 and CB2 were distributed in a complementary fashion. Double-immunostaining with an anti-CGRP antibody suggested the presence of cannabinoid receptors on small afferent peptidergic nerves. The abundant distribution of cannabinoid receptors on skin nerve fibers and mast cells provides implications for an anti-inflammatory, anti-nociceptive action of cannabinoid receptor agonists and suggests their putatively broad therapeutic potential.

Substance P and vasoactive intestinal peptide in rat small-bowel isografts

Background It is established that substance P (SP) is released by stimulation of nonadrenergic noncholinergic (NANC) excitatory nerves and vasoactive intestinal peptide (VIP) by stimulation of NANC inhibitory nerves. To evaluate the function of peptidergic nerves such as SP and VIP in small-bowel isografts, we examined the enteric nerve responses to SP and VIP in the isografted rat jejunum, using the normal rat jejunum as a control. Methods Orthotopic entire small bowel transplantation (SBT) with portocaval drainage was performed from Lewis rats to Lewis rats. Grafted tissue specimens were obtained 130 days after SBT (n = 9). As controls, normal segments of the jejunum were obtained from untransplanted Lewis rats (n = 22). A mechanograph was used to evaluate in vitro jejunal responses to electrical field stimulation of the enteric nervous system before and after treatments with various autonomic nerve blockers and neuropeptides (SP and VIP). Results SP concentration-dependently mediated the contraction reaction of NANC excitatory nerve in the isografted jejunum and to a lesser extent in the normal jejunum. In addition, there were significant diferences in the percentages showing contraction at 1 × 10 −8 and 1 × 10 −6g/mL SP between the normal and isografted jejunal muscle strips ( P < .05, respectively). VIP concentration dependently mediated the relaxation reaction of NANC inhibitory nerve in the normal jejunum and to a lesser extent in the isografted jejunum. In addition, there was a significant difference between the relaxation frequencies of the normal and those of isografted jejunal muscle strips at 1 × 10 −6 g/mL SP ( P < .01). Conclusions Contraction reactions of SP were observed in both the normal and isografted jejunum but were increased in the isografted jejunum. Relaxation reactions of VIP were also observed in both the normal and isografted jejunum but were decreased in the isografted jejunum. The increase of the effects of SP via NANC excitatory nerves and the decrease of the effects of VIP in mediating NANC inhibitory nerves may be largely related to the peristaltic abnormalities seen in the isografted LEW rat jejunum.

Stress exposure modulates peptidergic innervation and degranulates mast cells in murine skin

Stress is said to induce itchiness of the skin, exacerbate inflammatory skin diseases, and inhibit wound healing. Neuropeptides such as substance P (SP) may play a role in these processes. Recently, we were able to show that both stress or SP are associated with neurogenic inflammation and increased apoptosis in the murine hair follicle. Moreover, peptidergic cutaneous innervation is subject to lifelong plasticity due to its association with the cyclic growth of hair follicles. However, peripheral neuronal plasticity has never been reported in altered interactions between the nervous and immune systems under perceived stress. Here, we show for the first time plasticity of the cutaneous peptidergic innervation in response to stress. After exposure to sonic stress, the number of SP+ nerve fibers in the back skin of C57BL/6 mice with their hair follicles in the resting phase of the hair cycle (telogen—low numbers of nerve fibers) increased significantly. Such nerve fibers contacted mast cells more frequently. At the same time, the percentage of degranulated mast cells increased significantly associated with a rise in apoptotic cells in the skin. Increased numbers of peptidergic nerve fibers correlated with increased numbers of growth-associated protein 43 (Gap-43)+ nerve fibers, which is a marker for growing nerves. Thus, neuronal plasticity and increased neuro-immune interaction occur under stress and may alter inflammatory skin diseases and trophic functions in the skin where neurogenic inflammation plays a part.

Evidence for a Common Pattern of Peptidergic Innervation of Cnidocytes

Tentacles from representatives of all four classes of the phylum Cnidaria were examined using antibodies against the neuropeptides FMRFamide and RFamide to reveal the organization of neurons and nerve nets associated with cnidocytes. The tentacles of all species examined contained FMRFamide- or RFamide-immunoreactive neurons, in varying densities. In representatives from the Scyphozoa, Hydrozoa, and Cubozoa, the FMRFamide-immunoreactive neurons formed plexuses at the base of the cnidocyte assemblages; in anthozoans, the absence of discrete assemblies of cnidocytes precluded visual co-localization of cnidocytes and immunoreactive neurons. In all four classes, immunoreactive sensory cells connected these peptidergic nerve nets to the surface of the tentacle. These findings suggest that members of all four cnidarian classes share a common organizational pattern, and it is proposed that this peptidergic innervation may be involved in the chemosensory regulation of cnidocyte discharge.

Stress modulates peptidergic innervation and alters the cutaneous immune response: exacerbating pathomechanisms in atopic dermatitis?

Stress is said to induce itchiness of the skin and exacerbate inflammatory skin diseases such as atopic dermatitis. In this context, stress mediators such as the neuropeptide substance P play a role as immunmodulators and in a wider sense growth factors. For example, we were recently able to show that stress or treatment of mice with substance P is associated with mast cell degranulation, increased cutaneous inflammation and increased apoptosis in the hair follicle. However, local interactions between the nervous and immune systems, especially under perceived stress, have rarely been reported. Here, we show for the first time, that 24 and 48 h after sonic stress exposure, the number of SP‐immunoreactive nerve fibres in the back skin of C57BL/6 mice with all there hair follicles in the resting phase of the hair cycle (telogen, low numbers of cutaneous nerve fibres) increased significantly over non‐stressed mice with the strongest increase after 24 h. Such substance P immunoreactive nerve fibres contacted mast cells more frequently, which became significant after 48 h. At the same time, the percentage of degranulated mast cells increased significantly after 24 and 48 h with the strongest increase after 48 h when apoptotic cells also became significantly upregulated. The same stressor increased dermal infiltration, e.g. by eosinophils in C57BL/6 mice with experimentally induced allergic dermatitis over mice that were either stressed or had allergic dermatitis as well as over untreated controls. Increased infiltration was associated with increased epidermal thickness in stressed mice with allergic dermatitis and with an increased number of VCAM‐immunoreactive blood vessels. At the same time, the percentage of degranulated mast cells increased significantly, and the number of substance P‐immunoreactive peptidergic sensory nerve fibres decreased in the acute allergic dermatitis lesions. By semiquantitative RT‐PCR, allergic dermatitis increased cutaneous IL‐4 and to a lesser degree IFN‐γ production, but this was not affected by stress. Ultrastructural investigation showed unmyelinated peptidergic nerve fibres in a state of deterioration close to degranulating mast cells and eosinophils in the skin of stressed mice with allergic dermatitis, suggesting a decreased number of substance P‐immunoreactive nerve fibres due to active release of SP. This may lead to an upregulation of endothelial adhesion molecules and increased infiltration by immunocytes to the skin but at mRNA level does not alter the production of classical atopy‐related cytokines in skin. These data provide first evidence for stress‐induced exacerbation of cutaneous allergic diseases such as atopic dermatitis by local interaction of the peripheral nervous system with substance P.

Anatomy of efferent hepatic nerves

The role of neural elements in regulating blood flow through the hepatic sinusoids, solute exchange, and parenchymal function is incompletely understood. This is due in part to limited investigation in only a few species whose hepatic innervation may differ significantly from humans. For example, most experimental studies have used rats and mice having livers with little or no intralobular innervation. In contrast, most other mammals, including humans, have aminergic and peptidergic nerves extending from perivascular plexus in the portal space into the lobule, where they course in Disse's space in close relationship to stellate cells (fat storing cells of Ito) and hepatic parenchymal cells. While these fibers extend throughout the lobule, they predominate in the periportal region. Cholinergic innervation, however, appears to be restricted to structures in the portal space and immediately adjacent hepatic parenchymal cells. Neuropeptides have been colocalized with neurotransmitters in both adrenergic and cholinergic nerves. Neuropeptide Y (NPY) has been colocalized in aminergic nerves supplying all segments of the hepatic-portal venous and the hepatic arterial and biliary systems. Nerve fibers immunoreactive for substance P and somatostatin follow a similar distribution. Intralobular distribution of all of these nerve fibers is species-dependent and similar to that reported for aminergic fibers. Vasoactive intestinal peptide and calcitonin gene-related peptide (CGRP) are reported to coexist in cholinergic and sensory afferent nerves innervating portal veins and hepatic arteries and their branches, but not the other vascular segments or the bile ducts. Nitrergic nerves immunoreactive for neuronal nitric oxide (nNOS) are located in the portal tract where nNOS colocalizes with both NPY- and CGRP-containing fibers. In summary, the liver is innervated by aminergic, cholinergic, peptidergic, and nitrergic nerves. While innervation of structures in the portal tract is relatively similar between species, the extent and distribution of intralobular innervation are highly variable as well as species-dependent and may be inversely related to the density of gap junctions between contiguous hepatic parenchymal cells.

An ultra-stable non-coherent light source for optical measurements in neuroscience and cell physiology

We demonstrate that high power light-emitting diodes (LED’s) exhibit low-frequency noise characteristics that are clearly superior to those of quartz tungsten halogen lamps, the non-coherent light source most commonly employed when freedom from intensity variation is critical. Their extreme stability over tens of seconds (combined with readily selectable wavelength) makes high power LED’s ideal light sources for DC recording of optical changes, from living cells and tissues, that last more than a few hundred milliseconds. These optical signals (Δ I/ I 0) may be intrinsic (light scattering, absorbance or fluorescence) or extrinsic (absorbance or fluorescence from probe molecules) and we show that changes as small as ~8 × 10 −5 can be recorded without signal averaging when LED’s are used as monochromatic light sources. Here, rapid and slow changes in the intrinsic optical properties of mammalian peptidergic nerve terminals are used to illustrate the advantages of high power LED’s compared to filament bulbs.

Psychoneuroimmunology - mind-brain-immune interactions : mind and body : SAMJ forum

Psychoneuroimmunology (PNI) is the study of interactions between psychological, neuroendocrine and immune processes under basal, disease and therapeutic conditions. It expands the understanding of disease, recognising that psychological phenomena and social context can influence the aetiology and progression of and recovery from illness. While debate continues regarding the way in which intangible mental processes and identifiable physiological ones interact, there can be little argument that these psychological processes require an evolved nervous system, with certain neural networks — identified through imaging studies and neurological disease affecting the mind — related to mental and emotional functions. 1 The extension of the mind/brain relationship to include the immune system is predicated on the presence of multiple neuropeptides and their receptors in cells of the immune system, where they are produced and expressed de novo with high sequence homology to their neuroendocrine relatives, as well as structural links between lymphoid organs and noradrenergic and peptidergic nerve fibres. 2 Furthermore many immunopeptides and their receptors are produced de novo in discrete regions of the brain, most specifically the limbichypothalamic axis, where they may exert a neuromodulatory effect. 2 The functionality of the immune-brain-behavioural pathway has been well described during the acute phase or sickness response. The acute behavioural and physiological changes that regularly accompany infectious illness include, for example, fever, depression, social withdrawal, increased desire for sleep, decreased interest in food and perceptual changes. As part of the immune response to infection, interleukin-1 (IL-1) acts on IL-1 receptors in the vagus nerve and in the brain to mediate such sickness behaviours. 3

Peptidergic innervation in pars distalis of the human anterior pituitary

It has been previously shown that the peptidergic nerve fibers are present in the anterior pituitary of monkeys, dogs and rats. In our study, which is reported here, thick nerve fiber bundles, large numbers of peptidergic nerve fibers and their varicosities, which are substance P (SP)-, calcitonin gene-related peptide (CGRP)- and galanin (GAL)-immunoreactive (ir), are found in the human pituitary stalk. All these peptidergic nerve fibers run along the pituitary stalk and enter the pars distalis, and some GAL-ir nerve fibers even reach the center of the human anterior pituitary as well as in parenchyma of adenohypophysis. The number of SP-ir nerve fibers is much more than that of other kinds of peptidergic nerve fibers. All these peptidergic nerve fibers are mainly located in the medial part of the gland and distributed in its dorsal-posterior region. A substantial amount of these peptidergic nerve fibers with numerous varicosities are found to be close to the glandular tissue in the pars distalis of the human anterior pituitary. Furthermore, same SP-ir and CGRP-ir cells have been demonstrated in the pars distalis of the anterior pituitary. More or less, these peptidergic nerve fibers came also from the meningeal shell and enter the parenchyma of the anterior pituitary. Whatever the function of peptidergic nerve fibers in the human anterior pituitary might be, the concept that the adenohypophysis is regulated only hormonally by way of the portal system could be challenged.

The role of substance P in inflammatory disease.

The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin-1 receptor (NK-1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK-1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus-associated respiratory infection, non-productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK-1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK-1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK-1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease.

Development and distribution of mast cells and neuropeptides in human fetus duodenum.

To study the developmental regularities and heterogeneity of mast cells (MC) in human fetus duodenum and the distribution and developmental regularities of substance P(SP), calcitonin gene-related peptide (CGRP)-immunoreactive (IR) peptidergic nerves in fetus duodenum, as well as the relationship between MC, SP and CGRP- IR peptidergic nerves. Duodena from 21 cases of human fetus and one term infant were stained by hematoxylin-eosin (HE), toluidine blue (TB) and immunohistochemical avidin-biotinylated peroxidase complex (ABC) method. Lobe-shape intestinal villi in duodenum were already developed at the twelfth week. At the 21st wk, muscular mucosa appeared gradually, and four layers were observed in the wall of duodenum. TB staining showed that the granules in the immature MC were pale violet, while the mature MC were strong violet in color by TB staining. Connective tissue MC (CTMC) appeared occasionally in submucosa and muscular layer of duodenum at the 16th wk. While the mucosa MC (MMC) appeared at the 18th wk. At the 22nd wk, both CTMC and MMC were activated, and distributed in the surrounding blood vessels and ganglions. The verge of some MC were unclear, and showed degranular phenomena. At the 14th wk, SP and CGRP-IR nerve fibers and cells appeared in the myenteric and submucous plexuses in small intestine, and the responses were turn strongly. Neurons were light to deep brown, and nerve fibers were present as varicose and liner profiles. On the corresponding site of serial sections, SP and CGRP immunohistochemical reactions were coexisted in one nerve fiber or cell. Some of MC showed SP and CGRP-IR positive staining. There are two heterogeneous kinds of MC in duodenum, MMC and CTMC. MC might play an important role in regulating blood circulation and sensation.

Nerve fibres are required to evoke a contact sensitivity response in mice.

Previous work has indicated that the dermis and epidermis of skin contains abundant nerve fibres closely associated with Langerhans' cells. We have investigated whether these nerve endings are necessary for inducing and evoking a contact sensitivity (CS) response. Topical application of a general or a peptide (calcitonin gene-related peptide and substance P)-specific neurotoxin was employed to destroy the nerve fibres at skin sites subsequently used to induce or evoke the CS response. Elimination of nerve fibres abolished both induction and effector stages of the specific CS response. Denervation did not destroy the local Langerhans' cells, which were observed in increased numbers, or prevent them from migrating to lymph nodes. The local CS response was also abolished by systemic deletion of capsaicin-sensitive nerve fibres, suggesting that the loss of response was not non-specific but associated with the loss of specific nerve fibres. The results indicate that peptidergic nerve fibres are required to elicit a CS response and may be vital to the normal function of the immune system.

Jejunoileal bypass changes the duodenal cholecystokinin and somatostatin cell density.

In obese patients, jejunoileal bypass (JIB) has been used to induce weight reduction. Changes in the neuroendocrine system may be affected by the JIB-operation, because the proximal small intestinal mucosa has a rich supply of endocrine cells and peptidergic nerves. In 37 obese patients operated with JIB 1-30 years ago, small intestinal biopsies were taken at the duodeno-jejunal flexure, proximal to the anastomosis and from 5 unoperated obese persons and 20 normal weight patients. The tissue specimens were processed for immunocytochemical demonstration of cells/nerves containing: gastrin, cholecystokinin (CCK), secretin, gastric inhibitory peptide (GIP), motilin, somatostatin, serotonin, glicentine, peptide YY (PYY), neurotensin, vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and galanin. The number of different endocrine cell-types were counted per unit length of mucosa, and the density of the peptidergic nerves was assessed semiquantitatively according to a schematic scale. JIB-patients had an increased density of CCK and somatostatin cells in the duodenal mucosa. The CCK cells displayed a changed reaction pattern, with a greater cell number reacting with an antiserum directed towards a non-amidated mid-sequence of procholecystokinin compared with the other groups. In obese unoperated patients, the density of PYY and secretin cells was decreased compared with the JIB-patients and the density of the GIP cells compared with both other groups. JIB induces an up-regulation of somatostatin and CCK precursor-containing cells in the duodenal mucosa. The time duration after the JIB did not seem to influence the results.

Perineural capsaicin treatment attenuates reactive hyperaemia in the rat skin

The neural mechanisms of reactive cutaneous hyperaemia were studied by using a novel experimental approach: the simultaneous measurement of cutaneous blood flow by laser-Doppler flowmetry in adjacent innervated and chemodenervated skin regions of the rat hindpaw served by the same artery. Transient occlusion of the femoral artery (0.5–6 min) resulted in reactive hyperaemia that was greatly reduced in the chemodenervated region. After 3 min arterial occlusion, peak cutaneous blood flow was 109±13% vs. 53±7%* (% change from baseline, n=11, * P<0.05), and the total hyperaemic response was 110±21 vs. 52±12* (arbitrary perfusion units) in intact vs. chemodenervated skin regions, respectively. The findings provide clear evidence for the involvement of peptidergic capsaicin-sensitive afferent nerves in the mechanism of reactive cutaneous hyperaemia.

Peptidergic innervation of human esophageal and cardiac carcinoma.

To investigate the distribution of neuropeptide-immunoreactive nerve fibers in esophageal and cardiac carcinoma as well as their relationship with tumor cells so as to explore if there is nerve innervation in esophageal and cardiac carcinoma. Esophageal and cardiac carcinoma specimens were collected from surgical operation. One part of them were fixed immediately with 4 % paraformaldehyde and then cut with a cryostat into 40-microm-thick sections to perform immunohistochemical analysis. Antibodies of ten kinds of neuropeptide including calcitonin gene-related peptide (CGRP), galanin (GAL), substance P (SP), etc. were used for immunostaining of nerve fibers. The other part of the tumor specimens were cut into little blocks (1 mm(3)) and co-cultured with chick embryo dorsal root ganglia (DRG) to investigate if the tumor blocks could induce the neurons of DRG to extend processes, so as to probe into the possible reasons for the nerve fibers growing into tumors. Substantial amounts of neuropeptide including GAL-, NPY-, SP-immunoreactive nerve bundles and scattered nerve fibers were distributed in esophageal and cardiac carcinomas. The scattered nerve fibers waved their way among tumor cells and contacted with tumor cells closely. Some of them even encircled tumor cells. There were many varicosities aligned on the nerve fibers like beads. They were also closely related to tumor cells. In the co-culture group, about 63 % and 67 % of DRG co-cultured with esophageal and cardiac tumor blocks respectively extended enormous processes, especially on the side adjacent to the tumor, whereas in the control group (without tumor blocks), no processes grew out. Esophageal and cardiac carcinomas may be innervated by peptidergic nerve fibers, and they can induce neurons of DRG to extend processes in vitro.

Carotid body and glomus cells distributed in the wall of the common carotid artery in the bird.

In the bird the carotid body is located between the distal (nodose) ganglion of the vagus nerve and the recurrent laryngeal nerve at the beginning of the common carotid artery, that is, the organ is located at the cervicothoracic border. The chicken carotid body receives numerous branches from the vagus and the recurrent laryngeal nerves. In addition, dense networks of the peptidergic nerve fibers immunoreactive for substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), galanin, and neuropeptide Y (NPY) are distributed in and around the carotid body parenchyma. The substance P- and CGRP-immunoreactive fibers are derived from both the superior and inferior ganglia of the vagus nerve. The VIP-, galanin-, and NPY-immunoreactive fibers originate from the 14th cervical ganglion of the sympathetic trunk. The endocrine organs including the thyroid gland, parathyroid glands, carotid body, and ultimobranchial gland are situated as a continuous series along the common carotid artery. The organs are supplied with arteries arising as one trunk from the common carotid artery. Glomus cells are widely distributed not only in the carotid body but also in the wall of the common carotid artery and around the common trunk and its branches. The glomus cells of the chicken carotid body exhibit intense immunoreactivity for serotonin, tyrosine hydroxylase, and chromogranin A. The cells located in the wall of the common carotid artery further express NPY mRNA and peptide. In the chickens exposed to isocapnic hypoxia for 35 days, 3-4-fold increase of the carotid body volume is induced and the carotid body glomus cells show enhanced synthetic and secretory activities. On the other hand, the cells in the wall of the common carotid artery display little changes after the long-term hypoxia, having different functions from the carotid body. The carotid body rudiment is formed in the lateral wall of the third branchial artery. The neural cells immunoreactive for TuJ1, PGP 9.5, and HNK-1, which are continuous with the inferior vagal (nodose) ganglion, first surround and then invade both the carotid body rudiment and the other portions of the third branchial artery, becoming glomus cells.

Inhibition of gastric emptying and small intestinal transit by ethanol is mediated by capsaicin-sensitive afferent nerves.

The neural mechanisms involved in mediation of the inhibitory effects of ethanol on the gastric emptying and the small intestinal transit were studied in adult male rats. The gastrointestinal transit was determined by measuring the amount of phenol red recovered from the stomach and small intestine after intragastric administration. Spinal and/or vagal peptidergic afferent nerves were subjected to selective denervation by chemodenervation techniques using capsaicin, a potent and specific sensory neurotoxin. Intragastric administration of a 2.5 g/kg body weight dose of ethanol resulted in inhibition of the gastric emptying and the small intestinal transit. Prior systemic treatment with capsaicin, which defunctionalizes both spinal and vagal capsaicin-sensitive afferent nerves, abolished the inhibitory effect of ethanol on the gastrointestinal transit. Similarly, selective chemodenervation of the vagal afferents by perineural capsaicin treatment completely blocked the effect of ethanol. These observations furnish evidence indicative of the involvement of capsaicin-sensitive neural pathways, and in particular vagal afferent nerves, in the mediation of the inhibitory effect of large doses of ethanol on the gastrointestinal motility.