Substance P-immunoreactive Nerve Fibers Research Articles

Effect of capsaicin treatment or inferior alveolar nerve resection on dentine formation and calcitonin gene-related peptide- and substance P-immunoreactive nerve fibres in rat molar pulp

The aim of this study was to investigate whether decreased sensory innervation induced by capsaicin treatment or axotomy of the inferior alveolar nerve has an effect upon dentine formation in the rat first molar. Dentine formation was visualized by intravital injection of Procion brilliant Red H8BS and denervation was verified immunohistochemically for the neuropeptides calcitonin gene-related peptide (CGRP) and substance P. The observation times were 6 weeks for the capsaicin-treated group and 11 days for the axotomized group. Capsaicin injections caused a consistent reduction in numbers of CGRP- and substance P-immunoreactive fibres in the pulps and a somewhat smaller reduction in the periodontal tissues. Unilateral axotomy of the inferior alveolar nerve induced an almost complete loss of immunoreactive fibres in the pulp and in the mesial gingiva of the first molar. Dentine formation at the mesial pulp horn and at the central pulp floor was significantly reduced in both groups compared to controls. The results suggest that sensory neuropeptides such as CGRP and substance P may play a part in dentine formation.

Substance P- and vasoactive intestinal polypeptide-immunoreactive innervation in normal and inflamed pouches after restorative proctocolectomy for ulcerative colitis.

Recent studies suggest that the intestinal polypeptides substance P (SP) and vasoactive intestinal polypeptide (VIP) play a role in the bowel inflammatory processes. The aim of this study was to evaluate the distribution of SP and VIP immunoreactivities in the ileal pouch of the patients with ulcerative colitis (UC). Thirty-six patients underwent clinical evaluation, endoscopy, and histological examinations. Samples were taken from normal ileum (N = 9), ileum of UC patients (N = 9), normal ileal pouch (N = 9) and pouchitis (N = 9). SP- and VIP-containing nerve fibers were visualized in sections processed for immunofluorescence microscopy. The number and intensity of SP and VIP immunoreactivities were subjected to quantitative scoring. On samples from all groups lamina propria contained fibers showing bright immunofluorescence for SP and VIP. The number and intensity of SP immunoreactive nerve fibers were markedly increased in pouchitis as compared to normal pouch (P < 0.005), to ileum of UC patients (P < 0.001), and to normal ileum (P < 0.05). The number and intensity of VIP-immunoreactive nerve fibers in the lamina propria were markedly increased in pouchitis patients and in those having a normal pouch as compared to pooled values of ileum of UC patients and normal ileum (P < 0.05). The results suggest that SP, which may play a role in mediating inflammatory processes, is increased in pouchitis and that VIP, which may contribute to the regulation of intestinal motility, is increased in the pouch.

Electron Microscopic Observation of Substance P‐like Immunoreactive Nerve Fibres and Innervation in the Anterior Pituitary of Macaques

The anterior pituitary has recently been confirmed to be innervated by substance P-immunoreactive nerve fibres in the monkey and human. The present study investigated the morphology of the nerve fibres and their relationship with anterior pituitary gland cells in the macaque by means of immunoelectron microscopy. Many substance P-immunoreactive and unlabelled nerve fibres were distributed among the gland cells or formed nerve fibre bundles. These nerve fibres were unmyelinated and varicose, and contained a great many clear and/or large dense-cored vesicles. Substance P-immunoreactive cells were seen in the pars distalis of the anterior pituitary. Direct contacts between these nerve fibres and every cell type of the gland could be ascertained, including substance P-immunoreactive cells. Synaptoid contacts were seen among the substance P-immunoreactive varicosities and somatotropes, opiocortico-melanotropes and folliculostellate cells. Typical synapses were identified in somatotropes and opiocortico-melanotropes.

Substance P immunoreactivity in rat von Ebner's gland

The present immunohistochemical study revealed substance P-immunoreactive neuronal elements in the von Ebner's gland of rats. Immunoreactive ganglion cells were observed as single cells or groups of several immunoreactive ganglion cells among intra-lingual muscles, at the base of the vallate papillae and near the von Ebner's gland. Very numerous substance P-immunoreactive varicose nerve fibres ran closely associated with the serous cells and excretory duct cells, and were seen to run along blood vessels in the gland. Since substance P-immunoreactive ganglion cells were present near the glands, the immunoreactive varicose nerve fibres in the von Ebner's gland may be partly derived from the intra-lingual ganglion cells. These substance P-immunoreactive varicose nerve fibres may have an effect on the secretory activity of the serous cells and duct cells, and on the vasodilation of blood vessels of the von Ebner's gland. Actin immunoreactivity was seen in numerous myoepithelial cells embracing serous cells and duct cells, and in the smooth muscle cells of blood vessels of the gland. By using a double immunolabelling technique with anti-substance P and anti-actin sera, substance P-immunoreactive varicose nerve fibres were found to be in close contact with myoepithelial cells.

Effects of illumination and enucleation on substance-P-immunoreactive structures in subcortical visual centers of golden hamster and Wistar rat.

The undecapeptide substance P is found in different entities of the visual system that control eye movement and synchronize endogenous rhythms with the light cycle (i.e., superior colliculus, suprachiasmatic nucleus, intergeniculate leaflet). Immunocytochemical methods were used to compare the reactivity to substance P in the brain of five groups of golden hamsters and two groups of Wistar rats: (1) untreated hamsters kept under 14L:10D and sacrificed at noon; (2) identically maintained animals sacrificed at midnight; (3) enucleated animals kept under control conditions; (4) hamsters kept under constant darkness; (5) hamsters kept under the same conditions as the controls, but intraventricularly injected with colchicine. The results obtained in golden hamsters of groups (1) and (3) were compared with findings in Wistar rats treated accordingly [groups (6) and (7)]. Substance P-immunoreactive perikarya were found in the suprachiasmatic nucleus and superior colliculus of hamsters and Wistar rats. Substance P-immunoreactive nerve fibers were abundant in the hypothalamic area ventral to the paraventricular nucleus, in the intergeniculate leaflet, in some thalamic nuclei, and in the superior colliculus. Immunoreactivity to substance P in the suprachiasmatic nucleus and intergeniculate leaflet did not vary among the experimental groups. However, a conspicuous decrease in reactivity to substance P was observed in the superficial layers of the superior colliculus of enucleated hamsters and rats, compared with all other groups. These results indicate that substance P immunoreactivity in the superior colliculus, but not that in the suprachiasmatic nucleus or intergeniculate leaflet, depends on the integrity of the retinal projection.

Distribution of substance P immunoreactive nerve fibers in the tracheal submucosal gland of cats.

Immunohistochemistry combined with electron microscopy was employed to investigate the distribution of substance P-immunoreactive (SP-IR) nerve fibers in the tracheal submucosal gland of cats. The SP-IR nerve fibers were found to form a network around the glands. Numerous varicosities were also detected within the basement membrane of the acini and secretory tubules. All the intraglandular varicosities showed close spatial contact with serous cells, mucous cells, and myoepithelial cells. Our findings suggest that substance P-induced mucus secretion from tracheal submucosal glands in cats may be caused not only by a glandular contractile response of myoepithelial cells, but also by direct stimulation to both serous and mucous cells.

Characterization of antibodies to the rat substance P (NK-1) receptor and to a chimeric substance P receptor expressed in mammalian cells

Antibodies to neuropeptide receptors can be used to localize and characterize the receptors in tissues and cell lines. Two strategies were used to study the rat substance P receptor (SPR, NK-1) by immunological methods. First, a polyclonal antiserum was raised by immunizing rabbits with a peptide corresponding to the 15 amino acid residues (KTMTESSSFYSNMLA, SPR393-407) at the intracellular C-terminus of the rat SPR coupled to bovine thyroglobulin. An antiserum was obtained with a titer for half-maximal binding of 125I-SPR393-407 of 1:70,000. Nonradioactive SPR393-407 inhibited 50% of binding at a concentration of 10 pM. Binding of 125I-SPR393-407 to the antiserum was also displaced in a parallel manner by membrane proteins from tissues expressing high levels of the SPR (brain and submaxillary gland). Second, a chimeric SPR construct of a hydrophilic Flag peptide (DYKDDDDK) genetically engineered in sequence with the extracellular N-terminus of rat SPR was generated by polymerase chain reaction. The Flag-SPR chimera was expressed in rat kidney epithelial cells (KNRK) and judged to be fully functional, assessed by binding of 125I-substance P (apparent Kd of 5.63 nM) and calcium mobilization in response to substance P (EC50 of 0.66 nM). Antibodies to SPR393-407 and the Flag peptide stained the plasma membrane of KNRK cells expressing the native SPR or the Flag-SPR chimera. Staining was abolished by preincubation with SPR393-407 or the Flag peptide. Cells transfected with vector alone were unstained. The SPR antiserum recognized a broad protein band on Western blots of membranes prepared from cells expressing SPR but not from cells transfected with vector alone. The signal was quenched by preincubation of the antiserum with SPR393-407. By immunohistochemistry, the SPR antiserum was found to bind to neurons in the dorsal horn of the rat spinal cord and to ganglion cells in the myenteric plexus of the rat ileum near substance P-immunoreactive nerve fibers. Staining was abolished by preabsorption of the antiserum with SPR393-407. These antibodies can be used to localize the SPR in tissues and cells and to examine the function of the receptor in cell lines.

ヒト合谷相当部におけるＳｕｂｓｔａｎｃｅ‐Ｐ陽性線維とリンパ系の関連について

ヒト合谷相当部におけるＳｕｂｓｔａｎｃｅ‐Ｐ陽性線維とリンパ系の関連について

Anti-edema action of formoterol in rat trachea does not depend on capsaicin-sensitive sensory nerves.

The beta 2-adrenergic agonist formoterol has been shown to inhibit plasma extravasation in the respiratory mucosa associated with neurogenic inflammation as well as that caused by histamine or bradykinin. It is unknown whether these effects of formoterol are mediated through an action of sensory nerves or through a direct effect on the leaky blood vessels. In the present study we sought to determine whether capsaicin-sensitive sensory nerves are essential for the anti-edema effect of formoterol in the rat trachea. Substance P (5 micrograms/kg), PAF (hexadecyl-PAF, 5 micrograms/kg), or bradykinin (10 mg/kg) was injected intravenously to increase vascular permeability. The amount of plasma extravasation was measured with two tracers, Evans blue dye and Monastral blue pigment. The effectiveness of formoterol's anti-edema action was assessed in two groups of rats. One was pretreated with capsaicin to eliminate tachykinin-containing sensory nerves and another, the control group, was not pretreated. We found that in control rats formoterol inhibited to a similar extent the extravasation of Evans blue and Monastral blue caused by all three mediators. The highest intravenous dose of formoterol (10 micrograms/kg) reduced substance P-induced extravasation of Monastral blue by 59%, reduced PAF-induced extravasation by 74%, and reduced bradykinin-induced extravasation by 58%. Pretreatment of rats with a dose of capsaicin that eliminated at least 94% of the substance P-immunoreactive nerve fibers did not significantly reduce the effectiveness of formoterol against any of the mediators.(ABSTRACT TRUNCATED AT 250 WORDS)

Peptidergic innervation of human epicardial coronary arteries.

The peptidergic innervation of proximal (internal diameter, > 0.8 mm) and distal (internal diameter, < 0.8 mm) regions of human epicardial coronary arteries was investigated by means of immunohistochemical, chromatographic, radioimmunological, and in vitro pharmacological techniques. The use of an antiserum to the general neuronal marker protein gene product 9.5 revealed that the proximal part of epicardial arteries possessed a relatively sparse supply of nerve fibers forming a loose network in the adventitia. The perivascular network increased in density as the vessels were followed distally. In both proximal and distal regions, the majority of nerve fibers possessed neuropeptide Y and tyrosine hydroxylase immunoreactivity. Calcitonin gene-related peptide (CGRP)- and substance P-immunoreactive nerve fibers were very sparse in the proximal region of the arteries and increased in number distally. Only a few scattered vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers were detected in both arterial regions. The use of high-performance liquid chromatography and radioimmunoassay revealed that the immunoreactive material present in coronary artery extracts closely resembled synthetic peptides. An in vitro pharmacological method demonstrated that neuropeptide Y elicited no detectable response in either proximal or distal arterial segments. In contrast, CGRP, substance P, and VIP all produced a concentration-dependent relaxation of both arterial regions. CGRP and substance P were stronger and more potent than VIP. CGRP and substance P induced a more potent response in distal compared with proximal regions of the arteries. These results suggest that the peptidergic nerves supplying human large epicardial coronary arteries may be predominantly involved in mediating vasodilation.

Peptide-immunoreactive neurons and nerve fibres in lumbosacral sympathetic ganglia: Selective elimination of a pathway-specific expression of immunoreactivities following sciatic nerve resection in kittens

The distributions of peptide-immunoreactive nerve fibres and cell bodies in lumbosacral paravertebral sympathetic ganglia of young cats were analysed with antibodies to calcitonin gene-related peptide, enkephalin, neurotensin, somatostatin, substance P, galanin, neuropeptide Y and vasoactive intestinal polypeptide. Fairly dense networks of nerve fibres showing enkephalin-, neurotensin-, somatostatin- or substance P-like immunoreactivity were observed in the ganglia. Double-staining experiments revealed that enkephalin- and somatostatin-immunoreactive nerve fibres preferentially surrounded calcitonin gene-related peptide- and/or vasoactive intestinal polypeptide-immunoreactive cell bodies. Neurotensin- and substance P-immunoreactive nerve fibres were mainly associated with neurons showing neuropeptide Y and/or galanin-like immunoreactivity. Occasional nerves containing calcitonin gene-related peptide-, galanin-, neuropeptide Y- or vasocative intestinal polypeptide-like immunoreactivity were observed. These fibres did not seem to have any direct regional distribution within the ganglia. In kittens surviving for three months after early postnatal sciatic nerve resection, no calcitonin gene-related peptide-immunoreactive cell bodies could be detected in ganglia ipsilateral to the operation. In contrast, vasoactive intestinal polypeptide-like immunoreactivity, which partly co-exists with calcitonin gene-related peptide, was observed to the same extent as in control ganglia. Furthermore, almost all of the somatostatin-immunoreactive varicose nerve fibres had disappeared, whereas a fairly dense network of calcitonin gene-related peptide-immunoreactive nerve fibres could be observed. This change was paralleled by an increased content of nerve fibres that were immunoreactive to antibodies against the growth-associated protein GAP-43 (also known as B-50). The present findings suggest that experimental perturbations where postganglionic neurons are separated from their target areas by axotomy, not only induce differential changes in neurotransmitter expression in the principal ganglion cells, but also in preganglionic sympathetic neurons projecting to the ganglia. One possible explanation for the occurrence of an axotomy-induced network of calcitonin gene-related peptide-immunoreactive nerve fibres, is that extrinsic sensory nerve fibres grow into the ganglia after the sciatic nerve lesion. Thus, these findings seem to suggest one additional possibility with regard to the question of a possible interaction between sympathetic and sensory neurons after peripheral nerve injury.

Indications for a central innervation of the bovine pineal gland with substance P-immunoreactive nerve fibers

An antiserum, raised in rabbits, against substance P was used in an immunohistochemical investigation of the bovine pineal gland. A moderate innervation of all parts of the bovine pineal gland with subtance P-immunoreactive nerve fibers was demonstrated. The immunoreactive nerve fibers were located throughout the pineal gland, both perivascularly, intraparenchymally, and with few fibers in the pineal capsule. Within the habenular nucleus, a large number of substance substance P-immunoreactive perikarya were present. From these perikarya processes extended towards the pineal stalk and gland. Some substance P-immunoreactive nerve fibers were located in the stria medullaris and in the posterior commissure. The anatomical location of the substance P-immunoreactive nerve fibers in the pineal gland and stalk strongly indicates that, in this species, subtance P-immunoreactive pinealopetal nerve fibers originate from perikarya in the brain, probably from the medial habenular nucleus.

喉頭粘膜上皮のＳＰ，ＣＧＲＰ陽性線維に関する形態学的研究 種差について

This study was carried out to determine the different densities in laryngeal intraepithelium of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive (IR) nerve fibers in the dog, rat, guinea pig and cat. In the supraglottic and subglottic regions, the densities of SP and CGRP IR nerve fibers occured in decreasing order as follows: dog, rat, guinea pig and cat. Only a few fibers were found in the vocal folds of all species. We observed a greater density of CGRP IR nerve fibers than SP in all the animals studied. It was suggested that the difference in the distribution of SP and CGRP IR nerve fibers is related to differences in the sensory and reflex system of the larynx.

Effect of ageing on responses of nerve fibres to pulpal inflammation in rat molars analysed by quantitative immunocytochemistry

The response of sensory nerve fibres to inflammation in young adult rat molars has recently been shown to include increases in nerve sprouting and neuropeptide content. The objective was to evaluate neural responses to class V dental preparations in molars of old (1–2 yr) as compared with young adult rats (3–4 months). Tissues were investigated immunocytochemically 4 days post-injury for the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P. Quantitative image analysis of the material demonstrated that more immunoreactivity was present for CGRP than for substance P in intact control teeth for each age group. Four days after injury, both immunoreactivities were increased in pulp adjacent to the injury in both young and old teeth. The increase depended on at least three factors: (1) enhanced immunoreactivity of the nerve fibres; (2) increased terminal nerve sprouts near the injury and (3) elevated peptide content of the pulp tissue. Although the incidence of CGRP- and substance P-immunoreactive nerve fibres had decreased in older teeth, the proportional increases in both neuropeptides near the injury were greater in old than in young teeth, owing to a reduction in pulpal volume during ageing. Pulpal tissue was also immunostained for the low-affinity nerve growth factor receptor (p75-NGFR) as an index of pulpal ageing; and an extensive decrease was found in the old adult as compared to young adult rats. These results indicate that old rats maintain the capacity for nerve sprouting despite the decreases in p75-NGFR labelling of pulp cells, pulp volume and nerve fibre numbers that occur as part of dental ageing.

Neonatal capsaicin-treatment in mice: effects on pancreatic peptidergic nerves and 2-deoxy- d-glucose-induced insulin and glucagon secretion

It is not known whether sensory nerves are involved in the insulin, glucagon or glucose responses to autonomic nerve activation induced by 2-deoxy- d-glucose (2-DG). We therefore treated mice neonatally with capsaicin which permanently destroys sensory afferent nerve fibers. Immunohistochemistry of the pancreas at 13–14 weeks of age revealed a substantial reduction of calcitonin gene-related peptide (CGRP)-immunoreactive nerves and a partial reduction of substance P-immunoreactive nerves. In contrast, no effect was observed on galanin-immunoreactive nerves. At age 10–12 weeks, the mice were injected intravenously with 2-DG (500 mg/kg). In controls, 2-DG stimulated insulin and glucagon secretion and induced hyperglycemia ( P < 0.01). Capsaicin treatment partially reduced the glucose and glucagon responses to 2-DG ( P < 0.01). In contrast, the insulin response to 2-DG was not affected by capsaicin. It is concluded that the mouse pancreas contains capsaicin-sensitive sensory CGRP- and substance P-immunoreactive nerve fibers, whereas the galanin-immunoreactive nerve fibers are not sensitive to capsaicin. Furthermore, capsaicin-sensitive sensory nerve fibers are partially involved in 2-DG-induced glucagon secretion and hyperglycemia, whereas sensory nerves are not involved in 2-DG-induced insulin secretion.

Plasticity in expression of calcitonin gene-related peptide and substance P immunoreactivity in ganglia and fibres following guanethidine and/or capsaicin denervation.

This study was designed to investigate the effects of multiple denervation procedures on calcitonin gene-related peptide- and substance P-immunoreactive neurons in sympathetic and sensory cranial ganglia and in selected targets. Sympathectomy by long-term guanethidine treatment induced a pronounced increase in calcitonin gene-related peptide-immunoreactive and substance P-immunoreactive nerve fibres in all the tissues investigated, in contrast to a significant reduction of immunoreactive cell bodies. Neonatal capsaicin treatment abolished substance P immunoreactivity in many targets and caused a dramatic reduction of substance P-immunoreactive sensory nerve cell bodies; calcitonin gene-related peptide-immunoreactive nerve density was decreased, but the number of immunoreactive nerve cell bodies was unchanged. Guanethidine treatment of capsaicin-injected rats reversed the loss of calcitonin gene-related peptide-immunoreactive nerves, but not that of substance P-immunoreactive neurons. In the iris, capsaicin treatment had little effect on calcitonin gene-related peptide- and substance P-immunoreactive nerves, suggesting that in rats the majority of these fibres originate from capsaicin-insensitive neurons. The results suggest that the denervation procedures used in this study alter the synthesis and transport of neuropeptides in sensory neurons in conjunction with changes in the number of nerve fibres.

Guanethidine sympathectomy of mature rats leads to increases in calcitonin gene-related peptide and vasoactive intestinal polypeptide-containing nerves

Changes in the innervation of the heart (right atrium), mesenteric blood vessels, vas deferens and superior cervical ganglia have been examined following long-term sympathectomy of the mature rat. Patterns of innervation were investigated by histochemical and immunohistochemical techniques, while levels of noradrenaline and neuropeptides were measured by neurochemical assays. Large doses of guanethidine (80mg/kg) were given daily for four weeks to 12–14 week-old male rats which were killed at 18–20 weeks of age. Catecholamine-containing nerves were severely depleted or absent in all tissues, together with a reduction in noradrenaline content. Neuropeptide Y levels were depleted by 97% in vas deferens, 78% in mesenteric vein and 50% in right atrium and superior cervical ganglion. Increases in levels of calcitonin gene-related peptide were seen in the mesenteric vein (up seven-fold), superior cervical ganglia (up 11-fold) and vas deferens (prostatic portion up three-fold), which were also evident by assessment of immunolabelling of nerve fibres. Calcitonin gene-related peptide levels were not increased in the right atrium. In addition, an increase in vasoactive intestinal polypeptide-immunoreactive nerve fibre density was seen in the mesenteric artery and vas deferens, although no significant differences were observed in assays of vasoactive intestinal peptide levels in any tissue. No changes were seen in the innervation of any of the tissues by substance P-immunoreactive nerve fibres either by immunohistochemical or immunochemical assay assessment. This study indicates that there are selective changes in the mature nervous system in response to the loss of sympathetic nerves. Differences between these changes and the response of the developing nervous system to long-term sympathectomy are discussed.

Ultrastructural localization of somatostatin- and substance P-immunoreactive nerve fibers in the feline liver

The distribution and the possible source of somatostatin- and substance P-immunoreactive nerve fibers were studied in the liver of the cat by immunocytochemical techniques. Abundant substance P-immunoreactive and a moderate number of somatostatin-immunoreactive nerve fibers were found running around the blood vessels in the perilobular connective tissue. Some somatostatin-immunoreactive nerve cell bodies were also observed in the liver. A moderate number of somatostatin-immunoreactive nerve profiles were found inside the hepatic lobules along the sinusoid endothelial cells and the hepatocytes. The interspace between the axon and hepatocyte and endothelial cells membranes was about 20 nm. Cutting the extrinsic hepatic nerves resulted in marked reduction of substance P-immunoreactive nerves but only a slight reduction of somatostatin-immunoreactive nerves in the liver. These findings provide a morphological basis for the possibility that somatostatin and substance P may act as transmitters or neuromodulators on the neighboring smooth muscle cells of vessels and may regulate the function of the hepatocytes. It is also possible that some of these fibers serve sensory function along the blood vessels.

Endocrine cells and nerves in the stomach of the lizard Podarcis hispanica detected by immunocytochemistry

The general identification of endocrine cells in the stomach of the lizard Podarcis hispanica was carried out by their response to the Grimelius and Masson-Fontana techniques. 11 immunoreactive cell-types, positive for chromogranin-, serotonin-, caerulein/gastrin/ cholecystokinin (CAER/G/CCK)-, glucagon-like-peptide-1 (GLP-1)-. glucagon-, bombesin-,somatostatin-, pancreatic polypeptide (PP)-, peptide tyrosine tyrosine (PYY)-, neurotensin-and calcitonin gene related peptide (CGRP)- antisera were detected by immunocytochemical methods. Co-existence of glucagon with GLP-1, and PP with PYY were observed in some cells. Furthermore, immunoreactivities for members of gastrin and PP families were also found to co-exist in a few cells. In the muscular layer, vasoactive intestinal peptide (VIP)- and substance P-immunoreactive nerve fibers were also found.

Substance P and Neurokinin A in Human Nasal Mucosa

The tachykinins substance P (SP) and neurokinin A (NKA) were studied in human inferior turbinate nasal mucosa by radioimmunoassay, immunohistochemistry, and autoradiography and for their effect upon mucus release in an in vitro culture system in order to infer their potential functions in the upper respiratory tract. Similar amounts of SP (1.03 +/- 0.12 pmol/g wet weight; mean +/- SEM; n = 26) and NKA (0.76 +/- 0.23; n = 7) were found. NKA and SP immunoreactive nerve fibers were found in the walls of arterioles, venules, and sinusoids and as individual fibers in gland acini, near the basement membrane, and in the epithelium. [125I]SP bound to arterioles, venules, and glands. [125I]NKA bound only to arterioles. In short-term explant culture of fragments of human nasal mucosa, both 1 microM SP and 1 microM NKA stimulated release of [3H]glucosamine-labeled respiratory glycoconjugates. These results indicate that SP and NKA have similar distributions in nociceptive sensory nerves in human nasal mucosa. The distribution of [125I]SP binding sites is consistent with a role for SP as a vasodilator and mucous secretagogue. The presence of [125I] NKA binding sites on vessels suggests a primary role for NKA in regulating vasomotor tone.