Biomedical subjects

F Sundler

Publications and source records attributed to F Sundler.

At least 73 records · Page 4Linked to original sources

PubMed1998

Pituitary adenylate cyclase-activating peptide is upregulated in sensory neurons by inflammation.

The neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) is expressed in sensory neurons. Expression of several neuropeptides is up-regulated in sensory neurons following inflammation. To examine whether also PACAP expression is regulated by inflammation, PACAP expression in L5 dorsal root ganglion (DRG) was determined, using in situ hybridization, after unilateral adjuvant-induced inflammation in the rat paw. At 12 h and day 3, but not day 21, the percentage of neurons expressing PACAP mRNA was greater in the innervating L5 DRG. Similarly, PACAP mRNA expression in individual neurons was higher in the innervating L5 DRG at 12 h and day 3, but not day 21. Up-regulated PACAP expression following adjuvant injection suggests a role for PACAP in inflammation.

Animals↗

PubMed1998

PACAP and PACAP receptors in insulin producing tissues: localization and effects.

We have studied the localization, receptor occupancy and potency of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in insulin-producing tissues. Immunocytochemistry showed that PACAP-like immunoreactivity (PACAP-IR) was localized to pancreatic nerves with accumulation in intrapancreatic ganglia in both mouse and rat. In contrast, PACAP-IR could not be demonstrated in endocrine cells. Furthermore, in situ hybridization, using oligodeoxyribonucleotide probes recognizing mRNA for PACAP receptors, demonstrated that mouse and rat pancreas, and the insulinoma cell lines HIT-T15 and RINm5F, expressed both the PACAP type 1 and the VIP2/PACAP receptors. Moreover, both PACAP27 and PACAP38 dose-dependently (0.1 nM to 100 nM) and equipotently stimulated insulin secretion in isolated mouse and rat islets and in HIT-T15 and RINm5F cells. Furthermore, in mouse islets, vasoactive intestinal polypeptide (VIP) was of equal potency as PACAP at stimulating insulin secretion. In mouse, PACAP also stimulated insulin secretion in a subfraction of the isolated islets also at the low dose of 1 fM. Thus, (1) PACAP is exclusively a neuropeptide in the pancreas, (2) insulin-producing cells express PACAP type 1 and VIP2/PACAP receptors and (3) the two forms of PACAP equipotently stimulate insulin secretion. Based on these results, we suggest that PACAP is involved in the neural regulation of insulin secretion.

Animals↗

PubMed1998

Distribution and origin of nerve fibers in the rat temporomandibular joint capsule.

The distribution and origin of nerve fibers containing neuropeptides and NOS projecting to the temporomandibular joint capsule (TMJ) of the rat were studied by retrograde tracing in combination with immunocytochemistry. Numerous nerve fibers were seen in the TMJ as revealed by the neuronal marker protein gene product 9.5. Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP), calcitonin gene-related peptide (CGRP), and nitric oxide synthase (NOS) were seen in the synovial membrane, the joint capsule and entering the articular disc. Injection of the retrograde tracer True Blue (TB) into the TMJ resulted in the appearance of numerous labeled nerve cell bodies in the trigeminal and superior cervical ganglia, and moderate numbers in the nodose, the otic, the sphenopalatine, the stellate and the dorsal root ganglia at levels C2-C5. Most of the TB-labeled cell bodies in the superior cervical and stellate ganglia contained NPY. In the trigeminal ganglion, numerous TB labeled cell bodies contained CGRP and a minor population stored SP, a few cell bodies were seen to store NOS or PACAP. In the sphenopalatine and otic ganglia, TB labeled cell bodies contained NOS or VIP. In the nodose ganglion, labeled cell bodies contained CGRP; other labeled cell bodies harbored NOS. In the cervical dorsal root ganglia, the majority of the labeled cell bodies stored CGRP and smaller populations stored SP and PACAP. Thus, the innervation of the TMJ is complex and many different ganglia are involved.

Animals↗

PubMed1998

Pituitary adenylate cyclase activating polypeptide (PACAP) in the gastrointestinal tract of the rat: distribution and effects of capsaicin or denervation.

The expression of pituitary adenylate cyclase activating polypeptide (PACAP) was studied in the gastrointestinal tract (GI-tract) of normal rats using radioimmunoassay, chromatography, immunocytochemistry, and in situ hybridization. PACAP-38, PACAP-27, and PACAP-related peptide were demonstrated in all parts of the GI-tract, PACAP-38 being the predominant form confirmed by chromatography. PACAP-immunoreactive nerve fibers and nerve cell bodies were found in the myenteric ganglia throughout the GI-tract. PACAP-containing nerve cell bodies were also demonstrated in the submucous ganglia of the small and large intestine. The synthesis of PACAP in intrinsic neurons was confirmed by in situ hybridization. Double immunostaining showed that PACAP is present in calcitonin gene-related peptide-containing sensory nerve fibers as well as in vasoactive intestinal polypeptide (VIP)- or VIP/gastrin-releasing peptide (GRP)-containing (intramural) nerve fibers in the upper GI-tract and in anally projecting, intrinsic VIP-and VIP/nitric oxide syntase-containing nerve cell bodies and nerve fibers in the small and large intestine. Neonatal treatment with capsaicin significantly reduced the concentration of PACAP-38 in the esophagus, stomach, and colon. Extrinsic denervation decreased the PACAP-38 concentration in the stomach, while no change was observed in the small intestine. These results indicate that PACAP- immunoreactive nerve fibers in the GI-tract originate from both intrinsic (enteric) and extrinsic (presumably sensory) sources suggesting that PACAP may have diverse gastrointestinal functions.

Animals↗

PubMed1998

Gastric mucosal smooth muscles may explain oscillations in glandular pressure: role of vasoactive intestinal peptide.

BACKGROUND & AIMS: Oscillating (3-7 cycles/min) high pressures in gastric glands during acid secretion suggest the existence of rhythmically contracting mucosal muscles. The aim of this study was to study vasoactive intestinal peptide (VIP), an inhibitory neurotransmitter in the gastrointestinal tract, in relation to mucosal muscles, glandular pressure, and blood flow. METHODS: Rat, dog, and human mucosae were examined immunocytochemically for smooth muscle actin and VIP. Glandular pressure was measured using microelectrodes, red blood cell velocity (V[RBC]) was measured using a cross-correlation technique, and blood flow was measured using laser Doppler flowmetry in exposed gastric mucosa of thiobutabarbital sodium-anesthetized rats. RESULTS: Actin immunostaining showed muscle strands arising from muscularis mucosae, extending toward the gastric pits. VIP-immunoreactive nerve fibers were found in close relation to these muscles. VIP, administered intra-arterially close to the stomach (2 microg/kg bolus, followed by 10 microg x kg[-1] x h[-1]), significantly decreased glandular pressure from 18.2 +/- 1.6 to 8.9 +/- 1.6 mm Hg and almost eliminated the pressure oscillations. VIP infusion also abolished the oscillations in V(RBC) and significantly increased blood flow by approximately 35%. CONCLUSIONS: Contracting mucosal muscles may be responsible for oscillations in glandular pressure and possibly also in V(RBC). VIP probably relaxes these muscles.

Animals↗

PubMed1998

Changes in pituitary adenylate cyclase activating peptide and vasoactive intestinal peptide innervation of rat oxyntic mucosa during ulcer healing.

Pituitary adenylate cyclase activating peptide and vasoactive intestinal peptide belong to the same neuropeptide family. Both peptides are present in nerve fibers in the gastric wall and are thought to be involved in the regulation of inflammatory processes. Experimental ulcers were induced in the rat gastric mucosa by local application of acetic acid. During the healing process we examined the PACAP and VIP innervation by means of immunohistochemistry and in situ hybridization. The ulcer area was examined from day 1 to day 15 after ulcer induction. There was a marked depletion of PACAP in nerve fibers at the ulcer margin from day 1 and onwards. On day 10 and day 15, PACAP-immunoreactive nerve fibers could again be visualized at the ulcer margin. In contrast, VIP immunoreactive nerve fibers were present at the ulcer margin at all time points studied. From day 10 following ulcer induction PACAP- and VIP- immunoreactive nerve fibers were increased in frequency in the smooth muscle beneath the ulcer. An upregulation of VIP and PACAP mRNA was also demonstrated in the myenteric ganglia adjacent to ulcer. The present results indicate that neuronal PACAP and VIP react differently to the inflammation at the ulcer margin but similarly in the smooth muscle during the ulcer healing.

Animals↗

PubMed1998

Contribution of plasma-derived molecules to mucosal immune defence, disease and repair in the airways.

This review discusses recent observations, in health and disease, on the release and distribution of plasma-derived molecules in the airway mucosa. Briefly, the new data on airway mucosal exudation mechanisms suggest that the protein systems of plasma contribute significantly to the mucosal biology, not only in injured airways but also in such mildly inflamed airways that lack oedema and exhibit no sign of epithelial derangement. Plasma as a source of pluripotent growth factor, adhesive, leucocyte-activating, etc., molecules may deserve a prominent position in schemes that claim to illustrate immunological and inflammatory mechanisms of the airway mucosa in vivo.

Absorption↗

PubMed1998

Enteric neuronal plasticity and a reduced number of interstitial cells of Cajal in hypertrophic rat ileum.

BACKGROUND: Partial obstruction of the ileum causes a notable hypertrophy of smooth muscle cells and enteric neurones in the proximally located intestine. AIMS: To study the expression of neuromessengers in the hypertrophic ileum of rat as little is known about neuromessenger plasticity under these conditions. To investigate the presence of interstitial cells of Cajal (ICC) in hypertrophic ileum. METHODS: Ileal hypertrophy was induced by circumferential application of a strip of plastic film for 18-24 days. Immunocytochemistry, in situ hybridisation, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry, and ethidium bromide staining were used to investigate the number of enteric neurones expressing neuropeptides and nitric oxide synthase, and the frequency of ICC. RESULTS: In the hypertrophic ileum several neuronal populations showed changes in their expression of neuromessengers. Myenteric neurones expressing vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide, and galanin were notably increased in number. In submucous ganglia the number of VIP immunoreactive neurones decreased while those expressing VIP mRNA increased. NADPH diaphorase positive submucous neurones increased dramatically while the number of neuronal type nitric oxide synthase expressing ones was unchanged. The number of ICC decreased notably in hypertrophic ileum. CONCLUSION: Enteric neurones change their levels of expression of neuromessengers in hypertrophic ileum. ICC are also affected. The changes are presumably part of an adaptive response to the increased work load.

Animals↗

PubMed1998

Insulin secretion by gastrin-releasing peptide in mice: ganglionic versus direct islet effect.

Gastrin-releasing peptide (GRP) stimulates insulin secretion by a direct islet effect. In this study, we initially demonstrated, by immunocytochemistry of the mouse pancreas, GRP immunoreactive nerve fibers within exocrine tissue, islets, and intrapancreatic ganglia. A more pronounced GRP innervation was found in ganglia compared with in islets. We therefore studied whether indirect cholinergic mechanisms contribute to the insulinotropic action of GRP. In mice, the insulinotropic response to GRP (4.25 nmol/kg i.v.) was inhibited by the m3-selective, muscarinic receptor antagonist 4-diphenylacetoxy-N-methyl piperidine methobromide (4-DAMP, 0.21 mol/kg; by 68%, P < 0.05) and by the ganglionic blocker hexamethonium (28 mol/kg; by 98%, P < 0.05). In contrast, in isolated islets, 4-DAMP or hexamethonium (10 or 100 microM) did not inhibit GRP (100 nM)-induced insulin secretion. Furthermore, afferent denervation by neonatal capsaicin did not affect the insulin response to GRP. We conclude that the insulinotropic effect of GRP in the mouse is mediated by both direct islet effects and through activation, at the ganglionic level, of postganglionic cholinergic nerves. In vivo, the indirect cholinergic mechanism predominates.

Animals↗

PubMed1998

Impaired gastric acid secretion in gastrin-deficient mice.

To further understand the role of the peptide hormone gastrin in the development and function of the stomach, we have generated gastrin-deficient mice by gene targeting in embryonic stem cells. Mutant mice were viable and fertile, without obvious visible abnormalities. However, gastric function was severely affected by the loss of gastrin. Basal gastric acid secretion was abolished and could not be induced by histamine, carbachol, or gastrin. Histological analysis revealed alterations in the two cell types primarily involved in acid secretion, parietal and enterochromaffin-like (ECL) cells. Parietal cells were reduced in number with an accumulation of immature cells lacking H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase). ECL cells were positioned closer to the base of the gastric glands, with markedly lower expression of histidine decarboxylase. Gastrin administration for 6 days reversed the effects of the gastrin deficiency, leading to an increase in the number of mature, H(+)-K(+)-ATPase-positive parietal cells and a partial restoration of acid secretion. The results show that gastrin is critically important for the function of the acid secretory system.

Animals↗

PubMed1998

Immunohistochemical study of the innervation of the boundary area of the hard and soft palates of the rat.

The palatal mucosa plays an important role for patients using full dentures. The posterior ridge of the denture is designed to fit on the border between the hard and soft palates; accordingly, this boundary area is of importance when the outline of the denture is designed. In the present study, a rich supply of nerve fibers was found in the mucosa of the boundary area of the hard and soft palates of the rat. An immunocytochemical examination revealed nerve fibers containing protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP), substance P (SP), pituitary adenylate cyclase-activating peptide, vasoactive intestinal polypeptide (VIP), C-terminal flanking peptide of neuropeptide Y (c-PON), or nitric oxide synthase (NOS). Thin nerve fibers with PGP 9.5, CGRP, or SP penetrated into the epithelium, reaching beneath the cornified layer and terminated as free nerve endings. VIP-, c-PON- and NOS-containing nerve fibers were distributed in the connective tissue. Many of the VIP- and c-PON-containing nerve fibers were associated with blood vessels. In addition, nerve fibers containing PGP 9.5, CGRP, SP and c-PON were observed around, and penetrating into, the taste buds in the boundary area.

Animals↗

PubMed1998

Plasma-derived proteins in airway defence, disease and repair of epithelial injury.

One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.

Animals↗

PubMed1997

The effects of axotomy and preganglionic denervation on the expression of pituitary adenylate cyclase activating peptide (PACAP), galanin and PACAP type 1 receptors in the rat superior cervical ganglion.

The effects of axotomy, chemical sympathectomy and preganglionic denervation on the expression of the neuropeptides, pituitary adenylate cyclase-activating peptide (PACAP), galanin (GAL), and the PACAP type 1 receptor in the rat superior cervical ganglion (SCG) were investigated by immunocytochemistry, in situ hybridization and receptor autoradiography. An antibody recognizing the rat vesicular acetylcholine transporter (VAChT) was used for the detection of preganglionic cholinergic fibers. In the normal SCG, PACAP-immunoreactivity (-IR) was present in numerous, basket-forming, preganglionic nerve fibers, while very few SCG neurons expressed PACAP. GAL-IR was restricted to occasional neurons, and a few nerve fibers, most of which were, in addition, PACAP-IR. PACAP type 1 receptors were expressed in all nerve cell bodies. Axotomy resulted in a rapid and prominent upregulation of PACAP in a large number of nerve cell bodies. There was a large increase also in GAL expression in many nerve cell bodies. In contrast, there was a marked decline in PACAP type 1 receptor expression. Chemical sympathectomy by administration of the catcholaminergic neurotoxin, 6-hydroxydopamine (6-OHDA), gave rise to similar changes. Preganglionic denervation led to the disappearance of PACAP- and VAChT-IR baskets and to the upregulation of PACAP and GAL expression in neurons located close to the entrance of the sympathetic chain, whereas PACAP type 1 receptor expression was not affected. PACAP and GAL were coexpressed in most neurons after axotomy and chemical sympathectomy. Taken together, these results indicate that disruption of target contact and/or the infliction of an injury to the axons of the sympathetic neurons, rather than the preganglionic output, regulates the expression of PACAP, GAL and the PACAP type 1 receptor.

Animals↗

PubMed1997

Pituitary adenylate cyclase-activating peptide (PACAP) and PACAP type 1 receptor expression in regenerating adult mouse and rat superior cervical ganglia in vitro.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a regulatory peptide belonging to the vasoactive intestinal peptide (VIP) family, is widely distributed in the central and peripheral nervous system. Recent studies have shown that PACAP expression is upregulated in sensory neurons in response to axonal injury. Here we report that PACAP and PACAP type 1 receptors are located in rat and mouse superior cervical ganglia (SCG). PACAP-immunoreactivity (-IR) was demonstrated in preganglionic fibers, whereas only occasional PACAP-IR cell bodies could be observed. In situ hybridization histochemistry using 35S-labeled deoxyribonucleotide probes confirmed that PACAP mRNA was present only in occasional cell bodies. In contrast, PACAP type 1 receptor mRNA was expressed in virtually all cell bodies within the ganglia. After removal and culturing of the SCG for 24 h, there was a marked increase in PACAP mRNA, whilst PACAP type 1 receptor mRNA expression appeared to be downregulated in most nerve cell bodies except for a few scattered neurons displaying a strong upregulation. The total specific binding of PACAP to isolated SCG membranes as assayed by [125I]PACAP-27 binding showed an increase in SCG cultured for 48 h. PACAP-27 neither affected axonal outgrowth from the cultured SCG nor the survival of cells within the SCG. We conclude that PACAP and PACAP receptors are rapidly upregulated in sympathetic ganglia in response to axonal injury and that PACAP may play a role during nerve regeneration.

Animals↗

PubMed1997

Islet amyloid polypeptide and calcitonin gene-related peptide expression are upregulated in lumbar dorsal root ganglia after unilateral adjuvant-induced inflammation in the rat paw.

After unilateral adjuvant-induced inflammation, expression of neuropeptides believed to be involved in the inflammatory response, e.g. substance P and calcitonin gene-related peptide (CGRP), is upregulated in innervating sensory neurons. Islet amyloid polypeptide (IAPP) is structurally related to CGRP and constitutively expressed in sensory CGRP-containing neurons; the role of IAPP in sensory neurons is unknown. To examine whether IAPP could play a role in inflammation, IAPP expression in L5 dorsal root ganglion (DRG) and its distribution in the dorsal horn were investigated after unilateral adjuvant-induced inflammation in the rat paw and compared with CGRP, using in situ hybridization and immunocytochemistry. At 12 h and day 3, but not day 21, the percentage of nerve cell profiles expressing IAPP and CGRP mRNA was greater in the ipsilateral L5 DRG; these changes paralleled the occurrence of edema around the tarsotibial joint and a slight limp. IAPP expression in individual nerve cell profiles was higher in the ipsilateral L5 DRG at 12 h, but not at days 3 and 21; the corresponding CGRP mRNA level was higher at days 3 and 21. At day 3, the higher expression of IAPP and CGRP on the ipsilateral side was accompanied by increased numbers of immunoreactive DRG neurons and fibers in the spinal cord dorsal horn. Largely, expression of IAPP and CGRP seems to be co-ordinately regulated by localized inflammation, although the rapid, but transient, upregulation in DRG neurons of IAPP mRNA expression and the slower, but sustained, upregulation of CGRP mRNA expression may indicate dissociated regulation of the peptides. Thus, IAPP could play a role in the initial phase of localized inflammation.

Amyloid↗

PubMed1997

Distinct receptors mediate pituitary adenylate cyclase-activating peptide- and vasoactive intestinal peptide-induced relaxation of rat ileal longitudinal muscle.

Relaxant responses to pituitary adenylate cyclase-activating peptide (PACAP)-27, PACAP-38 and vasoactive intestinal peptide (VIP) were examined in rat ileal longitudinal muscle. PACAP-27 was much more potent than PACAP-38 and VIP, with PACAP-38 and VIP being equipotent. The relaxation induced by each of the peptides was unaffected by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) (10[-4] M), tetrodotoxin (10[-6] M) or atropine (10[-6] M). Pretreatment with apamin (10[-6] M) abolished the relaxations induced by PACAP-27, but not those induced by PACAP-38 or VIP. Pretreatment with neuropeptide Y (NPY) (10[-7] M) inhibited relaxations induced by VIP, but not those induced by PACAP-27 or PACAP-38. No cross-desensitization between PACAP-27 and VIP could be revealed. In conclusion, distinct receptors mediate PACAP- and VIP-induced relaxations of rat ileal longitudinal muscle. At least three different types of receptors may exist: (1) a PACAP-27 preferring receptor coupled to apamin sensitive Ca2+-dependent K+ channels, (2) a PACAP specific receptor activated by both PACAP-27 and PACAP-38 but not by VIP and (3) a VIP specific receptor regulated by NPY by yet unknown mechanisms.

Animals↗

PubMed1997

Dexamethasone induces neuropeptide Y (NPY) expression and impairs insulin release in the insulin-producing cell line RINm5F. Release of NPY and insulin through different pathways.

Neuropeptide Y (NPY) occurs in adrenergic as well as in non-adrenergic nerves innervating the islets of Langerhans and inhibits glucose-stimulated insulin secretion. Recently we demonstrated that NPY is expressed within islet beta cells of the rat pancreas following treatment with dexamethasone in vivo. In this study we examined the cellular expression of NPY following dexamethasone treatment of the insulin-producing cell line RINm5F, which under control conditions does not express or release NPY. The cells were cultured with or without dexamethasone (100 nM) for 5 days. Over the 5-day culture period, dexamethasone time dependently induced an increased release of NPY with a concomitant decrease in the release of insulin. Northern blot and in situ hybridization revealed a corresponding time-dependent increase in the amount of NPY transcripts and in the number of cells labeled for NPY mRNA, whereas immunocytochemistry for NPY revealed only a few immunoreactive cells, indicating a rapid release of the formed peptide. Following 5 days of culture with dexamethasone, acute stimulation with D-glyceraldehyde (10 mM) or KCl (20 mM) Ca2+ dependently stimulated the release of insulin. In contrast neither stimulation with D-glyceraldehyde or KCl nor removal of extracellular Ca2+ affected the release of NPY. Furthermore the D-glyceraldehyde- and KCl-induced increase in cytosolic Ca2+, evident in control RINm5F cells, was impaired after dexamethasone treatment. We conclude that RINm5F cells show steroid-sensitive plasticity and express NPY after dexamethasone treatment concomitantly with a decreased insulin secretion and impaired increase in cytosolic Ca2+ upon depolarization with KCl or stimulation with D-glyceraldehyde. We also conclude that NPY and insulin secretion are regulated differently and suggest that the inability of the removal of extracellular Ca2+ to inhibit NPY secretion and the failure of D-glyceraldehyde and KCl to stimulate NPY secretion reflect a constitutive release of this peptide from the cells in contrast to the regulated release of insulin.

Animals↗

PubMed1997

Capsaicin-evoked release of pituitary adenylate cyclase activating peptide (PACAP) and calcitonin gene-related peptide (CGRP) from rat spinal cord in vivo.

Capsaicin-evoked release of pituitary adenylate cyclase activating peptide (PACAP)-like immunoreactivity (LI) from rat spinal cord was examined in vivo. In anaesthetized rats, a catheter was inserted through the atlanto-occipital membrane into the subarachnoid space at the level of the sacral spinal cord for infusion of artificial cerebrospinal fluid. Another catheter was placed in the cisternal opening for outflow. Blood pressure was monitored and kept stable during the experiment. Perfusion samples were analyzed for PACAP and calcitonin gene-related peptide (CGRP) by radioimmunoassay. The addition of capsaicin (10 microM) to the perfusate elevated the concentrations of PACAP-27-LI in the artificial cerebrospinal fluid by 177%, PACAP-38-LI by 93% and CGRP-LI by 692%. In view of the presence of PACAP-immunoreactive nerve fibres in the superficial layers of the dorsal horn and the expression of PACAP in the small sized neurons in the dorsal root ganglia, the findings suggest that PACAP is released into the artificial cerebrospinal fluid from C-fibres in the spinal cord. PACAP conceivably plays a modulating role in nociception.

Animals↗