Existence and coexistence of calcitonin gene-related peptide (CGRP) and substance P in cerebrovascular nerves and trigeminal ganglion cells.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
F Sundler
Publications and source records attributed to F Sundler.
Comparative histochemical distribution of nerve fibres storing noradrenaline and neuropeptide Y (NPY) in human ovary, fallopian tube, and uterus.
Nerves containing noradrenaline were studied by formaldehyde-induced fluorescence and neuropeptide Y (NPY) was visualised by immunohistochemistry in the human ovary, Fallopian tube and uterus. All structures were richly supplied with noradrenergic fibres closely associated with the vascular and non-vascular smooth musculature. NPY-containing nerve terminals were consistently fewer, particularly in the ovary. The best developed nerve supply was found in the tubal isthmus and uterine cervix. Vessels were usually innervated by plexuses of nerves, containing NPY as well as noradrenaline. The discrepancy between the number of the two types of histochemically distinguishable nerves suggests that, if noradrenaline and NPY are co-localised in one and the same nerve, this is not a constant phenomenon in the human female reproductive tract.
Fallopian Tubes↗
Calcitonin gene-related peptide is present in mammalian cerebrovascular nerve fibres and dilates pial and peripheral arteries.
Calcitonin gene-related peptide (CGRP) is a novel 37-amino acid peptide occurring in neurones within sensory ganglia, in brain stem, as well as in the walls of blood vessels of peripheral organs. Pial arteries of cat showed a well-developed supply of CGRP-positive nerve fibres. The peptide was found to be a potent dilator of both pial and peripheral vessels of rabbit and cat, and of pial vessels from man. The dilatory effect was independent of the vascular endothelium and was not mediated through adrenergic, cholinergic or histaminergic smooth muscle receptors. The neurogenic vasoconstriction induced by electrical field stimulation was temporarily inhibited by CGRP, as studied in central ear arteries from rabbits. The results suggest that CGRP is a transmitter or modulator playing a role in the regulation of vascular tone.
Animals↗
Occurrence and distribution of calcitonin gene-related peptide in the mammalian respiratory tract and middle ear.
Nerve fibres displaying immunoreactivity to calcitonin gene-related peptide (CGRP) are abundantly distributed in the respiratory tract of man, dog, cat, guinea-pig, rat and mouse. Numerous fine, beaded CGRP fibres were seen in the middle ear mucosa, and a moderate supply was found in the ear drum. In the nasal mucosa and in the wall of the Eustachian tube CGRP fibres occurred around blood vessels, arteries in particular. A conspicuously rich supply of CGRP fibres was seen beneath and within the epithelium. In addition, a few fibres were seen in smooth muscle bundles and close to sero-mucous glands. In the tracheo-bronchial wall CGRP fibres were distributed beneath and within the epithelium, in vascular and non-vascular smooth muscle and sometimes close to small glands. A few CGRP-immunoreactive endocrine-like cells were, in addition, distributed in the tracheal epithelium of cat, rat and mouse. The trigeminal, spinal and nodose ganglia, studied in rats and guinea-pigs, harboured numerous CGRP-immunoreactive nerve cell bodies. The cervical sympathetic ganglia were devoid of immunoreactive neuronal perikarya. Surgical and chemical (6-hydroxydopamine treatment) sympathectomy did not affect the number and distribution of CGRP fibres. The distribution of CGRP fibres in the respiratory tract suggests that CGRP may take part in sensory transmission. In addition, CGRP may affect the regulation of local blood flow, smooth muscle tone and glandular secretion.
Animals↗
Origin and distribution of neuropeptide Y-, vasoactive intestinal polypeptide-and substance P-containing nerve fibers in the urinary bladder of the rat.
The origin and distribution in the urinary bladder of nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and substance P (SP) were investigated in rats. Experimental procedures comprised preganglionic decentralization or postganglionic denervation of the bladder and also chemical sympathectomy as well as capsaicin treatment of newborn rats. Nerve fibers containing NPY were richly distributed in the detrusor muscle and also in the pelvic ganglia. Numerous NPY-containing nerve cell bodies were found in pelvic ganglia. A rich occurrence of VIP fibers and a more sparse distribution of SP-containing fibers were also found in the bladder as well as a relatively rich representation of VIP-containing nerve cell bodies in the pelvic ganglia. After decentralization the intensity of VIP and NPY immunofluorescence increased in nerve cell bodies of the pelvic ganglia and in nerve fibers in the wall of the bladder. Postganglionic denervation, on the other hand, eliminated all peptides examined in the bladder wall. After postganglionic denervation the situation in the ganglia was approximately the same as after decentralization. Chemical sympathectomy (6-OHDA) did not seem to change significantly the frequency and distribution of VIP-, SP- and NPY-fibers in the muscle layer of the bladder or in the pelvic ganglia, while the NPY-containing nerve fibers in the submucosal layer and around blood vessels of the bladder disappeared. Adrenergic nerve fibers in the wall of the bladder (visualized by histofluorescence) were markedly reduced in number after administration of 6-OHDA.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Quinacrine accumulation in pancreatic islet cells of rat and mouse: relationship to functional activity and effects on basal and stimulated insulin secretion.
The fluorescent acridine derivative, quinacrine, was found to accumulate in rat and mouse pancreatic islet cells storing insulin, glucagon, pancreatic polypeptide, or somatostatin. Following administration of large doses of tolbutamide via an oro-gastric tube, the intensity of quinacrine fluorescence of insulin cells was substantially reduced. Similarly, the pancreatic insulin content was lowered. In contrast, the fluorescence intensity of the glucagon, pancreatic polypeptide and somatostatin cells appeared unaffected. Basal plasma insulin levels in the mouse were slightly elevated following quinacrine administration (25%). Glucose-stimulated insulin release was markedly enhanced (51%) in quinacrine-pretreated animals, whereas insulin release induced by cholinergic stimulation was unaffected. The results show that quinacrine accumulates in the various pancreatic islet cells. The drug seems to be confined to the secretory granules and affects the insulin response to glucose but not that to cholinergic stimulation, suggesting that these secretagogues act through different or partly different secretory pathways.
Animals↗
Nerve fibres containing peptide histidine isoleucine (PHI) in the respiratory tract.
Recent studies have indicated that vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are formed by cleavage of a common precursor protein. In the present study we have examined the distribution of nerve fibres displaying PHI-like immunoreactivity in the upper respiratory tract of several mammalian species including man. PHI fibres were found to have the same general distribution as previously described for VIP fibres. These fibres were distributed mainly in the subepithelial connective tissue around both seromucous glands and blood vessels. In the tracheal wall, PHI fibres were also seen in the non-vascular smooth muscle. Sequential immunostaining for PHI and VIP revealed co-existence of the two peptides in the same nerve fibres.
Animals↗
Spinal projections of hypothalamic histidine decarboxylase-immunoreactive neurones.
The existence of a histidine decarboxylase (HDC)-immunoreactive diencephalo-spinal pathway in the rat was demonstrated using an antiserum raised against HDC from fetal rat liver. HDC-immunoreactive nerve cell bodies were numerous in the ventral and lateral caudal hypothalamus. More caudally, in the mesencephalon, no cell bodies were observed but fairly many, transversely cut nerve fibres were found in association with the fasiculus longitudinalis medialis bilaterally. At the most caudal medullary level these longitudinally passing fibres became displaced ventrally to a position just laterally to the pyramidal decussation. In the spinal cord the fibres were more dispersed and rather sparse in most areas. The existence of a diencephalo-spinal HDC-immunoreactive pathway was verified by analyzing material from rats which had received injections of the retrograde fluorescent tracer True Blue into the cervical spinal cord. True Blue fluorescence and HDC immunofluorescence were found to coexist in a subpopulation of the HDC-immunoreactive neurones in the hypothalamus.
Animals↗
Peptide-containing nerve fibers in the stomach wall of rat and mouse.
Peptide-containing nerve fibers were found to be numerous in the glandular stomach of the rat and mouse. The immunoreactive neuropeptides demonstrated included vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), gastrin-releasing peptide (GRP), substance P (SP), enkephalin, somatostatin, cholecystokinin, and neuropeptide Y (NPY). The density and distribution of the various peptide-containing fibers did not differ overtly between the pyloric and oxyntic gland areas except for the GRP fibers, which were fewer in the pyloric than in the oxyntic mucosa. The entire VIP nerve fiber population was found to also contain PHI. Immunoreactive NPY was found to occur in the VIP/PHI fibers (VIP/PHI/NPY fibers) in the smooth muscle and intramural ganglia of both rat and mouse and in the mucosa of the mouse. Mucosal VIP/PHI fibers in the rat did not contain any NPY-like material. Perivascular NPY fibers in both species and mucosal NPY fibers in the rat did not contain VIP or PHI. The mucosa harbored numerous GRP fibers and VIP/PHI (rat) or VIP/PHI/NPY (mouse) fibers, and a modest number of NPY (rat) and SP fibers. In the submucosa the peptide-containing nerve fibers were found mainly in the ganglia and around blood vessels. Blood vessels received a rich supply of NPY fibers; the number of perivascular VIP/PHI, GRP, and SP fibers was much lower by comparison. The smooth muscle and myenteric ganglia harbored not only VIP/PHI/NPY, GRP, and SP fibers but also enkephalin, somatostatin, and cholecystokinin fibers. Gastrin-releasing peptide, VIP/PHI/NPY, SP, and enkephalin nerve cell bodies occurred in the myenteric ganglia. As studied in the rat, vagal denervation did not affect the density and distribution of the various peptide-containing nerve fibers. After sympathectomy, mucosal and perivascular NPY fibers disappeared. The other types of peptide-containing nerve fibers were not affected.
Animals↗
Regulatory peptides in the lower esophageal sphincter of man.
Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.
Adolescent↗
Neuropeptide Y-like immunoreactivity in perivascular nerve fibres of the guinea-pig.
The distribution of perivascular nerve fibres displaying neuropeptide Y-like immunoreactivity was studied in the guinea-pig. Generally, neuropeptide Y fibres were numerous around arteries and moderate in number around veins. In the heart, immunoreactive fibres were numerous in the auricles and the atria (epi- and endocardium) whereas the ventricles had a more scarce supply. The coronary vessels were richly supplied with fibres. Around large elastic and muscular arteries the fibres formed well developed plexuses. Small arteries in the respiratory tract, the gastrointestinal tract and the genito-urinary tract received a particularly rich supply. In the liver, spleen and kidney only few perivascular fibres were seen. Since immunoreactive fibres around blood vessels disappeared upon surgical or chemical sympathectomy, and sequential immunostaining with antisera against dopamine-beta-hydroxylase (a marker for adrenergic neurons) and against neuropeptide Y revealed their co-existence, it is concluded that neuropeptide Y fibres around blood vessels are sympathetic and adrenergic.
Animals↗
Innervation of human omental arteries and veins and vasomotor response to noradrenaline, neuropeptide Y, substance P and vasoactive intestinal peptide.
Human omental arteries and veins are supplied with nerve fibers containing noradrenaline (NA) and neuropeptide Y (NPY); these two agents probably co-exist in perivascular sympathetic nerve fibers. Substance P (SP)- or vasoactive intestinal peptide (VIP)-containing fibers could not be detected. In studies on isolated omental vessels NA produced constriction. The results of blockade experiments suggest that human omental arteries are equipped predominantly with alpha 1-adrenoceptors and omental veins with a mixture of alpha 1- and alpha 2-adrenoceptors. NPY at a concentration of 10(-7) M or higher had a weak contractile effect on veins and virtually no effect on arteries. NPY at a concentration of 3 X 10(-8) M shifted the NA concentration response curve to the left in arteries (pD2 = 5.8 for NA versus 6.6. for NA in the presence of NPY; P less than 0.001) but not in veins. Both SP and VIP relaxed arteries precontracted with NA or prostaglandin F2 alpha (PGF2 alpha). The potency of SP as a relaxant agent was similar in arteries and veins; the effect of VIP was elicited at lower concentrations in veins than in arteries.
Aged↗
PYY-like peptides in the central and peripheral nervous system of a frog and a lizard.
PYY-immunoreactive material was detected in endocrine cells in the gut of a lizard, Lacerta vivipara, and a frog, Rana temporaria. The findings are consistent with other reports on reptiles, amphibians and higher species. In addition, however, PYY-like material was found in neuronal elements both in the gut and in the brain. High performance liquid chromatography of frog brain extracts showed the PYY-like material to elute in one minor fraction (eluting position similar but not identical to that of porcine synthetic PYY) and two major fractions (distinct from PYY and probably representing smaller and more hydrophobic PYY-like peptides).
Animals↗
Two distinct VIP precursors in cartilaginous fish?
In the ray gut immunoreactive VIP has a dual localization in endocrine cells and in nerve fibers. Immunoreactive VIP and PHI were found to co-exist in the same nerve fibers. This is predictable, since VIP and PHI derive from the same precursor. However, PHI could not be demonstrated in the VIP immunoreactive endocrine cells. Chromatographic analysis (high performance liquid chromatography) of extracts of the gut revealed two different molecular forms of VIP, one large peak with an elution position similar to that of authentic porcine VIP and a minor peak with a different elution position. The results suggest either the existence of different precursors for VIP in endocrine cells and in neurons, or the different processing of the same precursor in neurons and endocrine cells.
Animals↗
Galanin nerve fibers in the rat gut: distribution, origin and projections.
Galanin, a 29 amino acid peptide, was recently isolated from the porcine gut. Immunocytochemistry revealed a dense network of galanin-immunoreactive nerve fibers in the submucosa, smooth muscle layers and intramural ganglia throughout the rat gastrointestinal tract. In the smooth muscle the density of innervation was lower in the colon than in the small intestine. In the mucosa galanin-immunoreactive fibers were quite numerous in the small intestine, less numerous in the large intestine and rare in the stomach. A moderate number of galanin-immunoreactive nerve cell bodies could be detected in the myenteric ganglia throughout the digestive tract and in the submucous ganglia of the intestines. Enteric galanin-immunoreactive fibers seem to be intrinsic to the gastrointestinal tract since their distribution and frequency were unaffected after extrinsic denervation (chemical sympathectomy, vagal denervation or clamping of nerves running within the mesenterium). Myectomy at the mid-jejunal level resulted in a total loss of galanin-immunoreactive nerve fibers 5 mm anally to the lesion with a gradual return of galanin-immunoreactive fibers up to 15-20 mm further anally; there was no overt loss of fibers orally. The findings indicate that myenteric galanin-immunoreactive neurones issue long descending projections that terminate either within the myenteric ganglia or in the smooth muscle.
Animals↗
Endocrine tumors of the ileum. Cytochemical and clinical aspects.
Sixteen patients with endocrine ileal tumors and liver metastases were analyzed with regard to the size, multicentricity, and growth pattern of the primary tumor, the occurrence of carcinoid syndrome, as well as the concentrations of serotonin and substance P (SP) in blood, 5-hydroxy-indole-acetic acid (5-HIAA) in urine, and the course of the disease. Excised specimens from the tumors were immediately processed for immunocytochemical investigations of the presence of neurohormonal peptides, using a broad spectrum of antisera and optimal histoprocessing techniques. In all patients the serotonin levels in blood and/or the 5-HIAA in urine were high. The SP concentration in plasma was markedly elevated in all but two of the ten patients investigated in this respect. A mixed growth pattern prevailed in the tumors of 7 patients with fatal disease. Serotonin cells were found in all tumors and SP-immunoreactive tumor cells in all but one; one of the carcinoids also contained a few tumor cells displaying enkephalin immunoreactivity. In conventionally fixed and paraffin embedded specimens of the same tumors usually no immunoreactive tumor cells at all could be demonstrated, showing that SP is among the peptides vulnerable to poor histotechniques. Nevertheless, SP, together with serotonin, constitute reliable clinical tumor markers for ileal carcinoids.
Adult↗
Levels of neural vasoactive intestinal polypeptide in rat uterus are markedly changed in association with pregnancy as shown by immunocytochemistry and radioimmunoassay.
Immunocytochemical studies have shown that the rat uterus is well innervated by nerve fibers containing vasoactive intestinal polypeptide (VIP). The fibers were associated with both vascular and nonvascular smooth muscle cells, and they were somewhat more numerous in the cervix compared to the uterine horns. This was confirmed in radioimmunologic determinations. Pregnancy induced a marked, almost 50% reduction in the total content of VIP in the uterine horns, which was associated with an almost complete disappearance of immunocytochemically visible nerve fibers in this part of the uterus. The innervation normalized within 25 days following delivery. Less marked changes occurred in the VIP innervation of the cervical region, where the concentration of the peptide was reduced mainly as a result of the increased tissue weight during pregnancy.
Animals↗
Galanin: neuromodulatory and direct contractile effects on smooth muscle preparations.
The effects of galanin, a newly isolated neuropeptide, and of a galanin fragment (galanin 1-10) were studied on various smooth muscle preparations in vitro. Direct motor effects as well as effects on electrically induced (neuronally mediated) responses (neuromodulatory effects) were observed. Both gatanin and galanin 1-10 evoked a strong contractile response in rat jejunal longitudinal muscle. This effect was a direct one on the smooth muscle. Addition of galanin to guinea-pig taenia coli inhibited the contractile response to electrical stimulation, mediated by endogenous substance P and acetylcholine. In the rabbit iris sphincter, galanin reduced the acetylcholine-mediated but not the substance P-mediated contraction evoked by electrical stimulation. The neuromodulatory effects seem to be presynaptic and require the whole or possibly only the C-terminal part of the galanin molecule, since galanin 1-10 was ineffective. Rabbit femoral artery and vein, gastroepiploic and basilar arteries and guinea-pig trachea and main bronchi did not respond to either galanin or galanin 1-10.
Animals↗