Biomedical subjects

Rolf Uddman

Publications and source records attributed to Rolf Uddman.

12 recordsLinked to original sources

PubMed2003

Nociceptin immunoreactivity and receptor mRNA in the human trigeminal ganglion.

Nociceptin is a peptide transmitter belonging to the opioid family. Nociceptin has recently attracted considerable interest since it appears to exhibit a number of differences to the other opioids. In the present study, we used a nociceptin antibody to map the distribution of nociceptin in the human trigeminal ganglion. In addition, we studied the nociceptin receptor at mRNA levels by RT-PCR and the vasomotor response to nociceptin in human cerebral vessels using a sensitive in vitro method. About 70% of all neuronal cells in trigeminal ganglia were nociceptin immunopositive. Nociceptin was predominantly (78%) expressed in medium-sized cells (30-60 microm). Nociceptin also distributed in small-sized cells (14% of positive cell bodies; <30 microm) and in large-sized cells (8% of positive cell bodies; >60 microm). Double immunostaining showed that in the human trigeminal ganglion nociceptin colocalized with calcitonin gene-related peptide (CGRP), substance P (SP), nitric oxide synthase (NOS) or pituitary adenylate cyclase activating peptide (PACAP). About 61% of nociceptin positive cells contained CGRP, 54% contained SP, 50% contained NOS and 68% contained PACAP. Immunoreactivity to nociceptin was not detected in human cerebral blood vessels. Reverse transcriptase-polymerase chain reaction detected the expression of nociceptin receptor mRNA in trigeminal ganglia but not in basilar arteries. To further examine whether there are functional nociceptin receptors in human cerebral arteries, a pharmacological study was done, where cerebral arteries revealed strong contractions to 60 mM K(+) and U466166 and strong relaxation to CGRP. Nociceptin failed to elicit contraction or relaxation. In conclusion, nociceptin is expressed in human trigeminal ganglia but not in cerebral blood vessels. Nociceptin is colocalized with CGRP, SP, NOS and PACAP. Nociceptin receptor mRNA is expressed in human trigeminal ganglia but not in basilar arteries. The functional role of nociceptin may be at the presynaptic level.

Aged↗

PubMed2002

Capsaicin receptor immunoreactivity in the human trigeminal ganglion.

The cloned capsaicin receptor, also known as vanilloid receptor subtype 1 (VR1) receptor, has been demonstrated to be an integral membrane protein with homology to a family of putative store-operated calcium channels. The VR1 receptor is activated not only by capsaicin but also by noxious heat and protons, and therefore it is suggested as a molecular integrator of chemical and physical stimuli that elicit pain. In the present study, indirect immunofluorescence detected a small number of neurons that are VR1 receptor immunoreactive (ir) (171 versus 1038 or 16% of all neuronal cell bodies) in the human trigeminal ganglion (TG). In addition, RT-PCR confirmed the presence of VR1 mRNA in the human TG. It has been hypothesized that TG neuronal cell bodies are the source of capsaicin-stimulated release of calcitonin gene-related peptide (CGRP), and hence co-localization experiments were performed. Around 10% of the VR1 receptor-ir is expressed on neurons that contain CGRP-ir (ten among 74) in the human TG, indicating that capsaicin may act through the VR1 receptor to modulate the release of CGRP and in turn to modulate pain. We observed that 8% of the VR1 receptor-ir neuronal cell bodies contain substance P-ir and 5% nitric oxide synthase. Capsaicin can release nitric oxide, CGRP and substance P from sensory nerves and contribute to central sensitization.

Adult↗

PubMed2002

Neuropeptide Y Y1 and neuropeptide Y Y2 receptors in human cardiovascular tissues.

mRNA encoding the human NPY Y1 and NPY Y2 receptors were detected in cerebral, meningeal, and coronary arteries using reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, the trigeminal and superior cervical ganglia were positive for both receptors. In some arteries and in SK-N-MC cells only mRNA encoding the NPY Y1 was detected. Besides the expected NPY Y1 PCR products, an additional 97 bp longer amplicon originating from an alternative splicing event was found in most tissues studied. Antibodies directed against the NPY Y1 receptor revealed immunostaining mainly in the smooth muscle layer of blood vessels whereas antibodies against the NPY Y2 receptor showed immunostaining in nerve cell bodies.

Alternative Splicing↗

PubMed2002

Does nociceptin play a role in pain disorders in man?

Nociceptin-immunoreactive cellbodies were detected in the human trigeminal ganglion, while no such fibers were identified in the temporal artery or in dermal tissue from the neck region. In four healthy subjects receiving nociceptin into the temporal muscle in an open labeled design no pain was detected. In 10 healthy subjects who received 200pmol of nociceptin into tender non-dominant trapezius muscles in a placebo-controlled, randomized, balanced, and double-blinded design local tenderness increased (P=0.025) while no pain was noted. Thus, the action of nociceptin should be searched for in the trigeminal ganglion and/or in the central nervous system (CNS).

Adult↗

PubMed2002

PACAP enhances the expression of CD11b, CD66b and CD63 in human neutrophils.

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide with strong bronchodilator capacity, present in the human airways. There is recent evidence that PACAP decreases the release of proinflammatory cytokines. We have previously shown that PACAP inhibits neutrophil chemotaxis, but altogether little is known about the effects of PACAP on granulocytes. The present study was designed to investigate if PACAP and the closely related peptide vasoactive intestinal peptide (VIP) could affect the cell surface expression of CD11b, CD63 and CD66b in human neutrophils. Neutrophils isolated from 12 healthy blood donors were incubated with either PACAP or VIP, and the expression of neutrophil cell surface markers was assessed using flowcytometry. Neutrophils incubated with PACAP38 exhibited a marked, concentration-dependent increase in their expression of CD11b, CD63 and CD66b. In contrast, neutrophils incubated with VIP showed no increase of the investigated surface markers. This indicates a role for PACAP in granulocyte activation, mediated via a pathway not shared with VIP. Together with the previously presented data on leukocyte migration it suggests that PACAP acts as a regulator of neutrophil inflammation.

Antigens, CD↗

PubMed2002

An assay to evaluate the long-term effects of inflammatory mediators on murine airway smooth muscle: evidence that TNFalpha up-regulates 5-HT(2A)-mediated contraction.

1. Asthma research is arguably limited by an absence of appropriate animal models to study the pharmacology of inflammatory mediators that affect airway hyperresponsiveness and remodelling. Here we assessed an assay based on mouse tracheal segments cultured for 1-32 days, and investigated contractile responses mediated by muscarinic and 5-hydroxytryptamine (5-HT) receptors following long-term exposure to tumour necrosis factor-alpha (TNFalpha). 2. Following culture, in the absence of TNFalpha, maximum contractile responses to KCl and carbachol were similar, with an increase in response up to day two and a decrease to a stable level after 8 days. Maximal relaxations to isoprenaline were not affected by the culture procedure. The potency of KCl and isoprenaline increased throughout the study. DNA microarray data revealed that global gene expression changes were greater when tissues were introduced to culture than when they were maintained in culture. The morphology of smooth muscle cells was maintained throughout the culture period. 3. 5-HT induced a weak contraction in both fresh and cultured (up to 8 days) segments. Culture with TNFalpha produced a time- and concentration-dependent increase in the maximal contraction to 5-HT, evidently mediated by 5-HT(2A) receptors, whereas, the potency for carbachol was reduced. 4. In conclusion, the phenotype of airway smooth muscle remained largely intact during the culture period, even though minor changes were obtained during the first days of culture. The time-dependent effect of TNFalpha indicates the importance of studying the long-term effect of cytokines on the smooth muscle cells in relation to airway hyperresponsiveness and remodelling.

Animals↗

PubMed2002

Heme oxygenase and nitric oxide synthase in human middle ear epithelium indicates local carbon monoxide and nitric oxide production.

The gas mixture of the middle ear differs from that of the atmosphere, a fact that has been attributed to gas exchange across the middle ear mucosa. Several diseases of the middle ear seem to be related to impaired ventilation together with conjunctional changes in pressure and gas composition. Carbon monoxide (CO) and nitric oxide (NO) have recently been shown to be endogenously produced in the human lung as well as in the nasal airways. The production of CO and NO is enzymatically regulated by heme oxygenase (HO) and NO synthase (NOS), respectively. These enzymes display isoforms that are both constitutively expressed [HO-2, endothelial NOS (eNOS), neuronal NOS (nNOS)] and inducible [HO-1, inducible NOS (iNOS)] following different types of stimulation. The present study was designed to investigate the presence of HO-1, HO-2 and eNOS in the middle ear epithelium, using immunocytochemistry. Specimens from human middle ear mucosa obtained at autopsy and during surgery revealed HO-1-, HO-2- and eNOS-like immunoreactivity, indicating the possibility of local CO and NO production in the middle ear. If this assumption is true, it may affect our understanding of middle ear physiology and give new insights into the mechanisms behind middle ear pathology.

Carbon Monoxide↗

PubMed2002

Epithelial cells in nasal fluids from patients with allergic rhinitis: how do they relate to epidermal growth factor, eosinophils and eosinophil cationic protein?

The nasal epithelium protects the underlying tissue from damage. Epithelial cell growth is controlled by epidermal growth factor (EGF) and is possibly affected by toxic proteins, e.g. eosinophil cationic protein (ECP). The aims of this study were to examine nasal fluid epithelial cell counts and their relations to EGF, eosinophils and ECP in 23 patients with seasonal allergic rhinitis and 20 healthy controls. Nasal fluid epithelial cell counts were lower in patients than in controls. EGF levels did not differ between patients and controls, and correlated with epithelial cell counts in controls but not in patients. Eosinophils and ECP were higher in patients than in controls, but did not correlate with epithelial cell counts. The role of growth factors, such as EGF, in regulating epithelial cells merits further study.

Adolescent↗

PubMed2002

A decrease in maxillary sinus pressure, as seen in upper airway allergy or infection, results in an increase in upper airway nitric oxide levels.

The paranasal sinuses are connected to the nasal cavity via small osties. Ostial occlusion, caused by mucosal swelling, will result in a slowly increasing negative pressure inside the sinus cavity. In parallel, the oxygen content in the sinus will decrease, resulting in the development of relative hypoxia. Hypoxia is a powerful inducer of nitric oxide (NO) synthase, and inducible NO synthase has been shown to be present in considerable amounts in the upper airways, including the sinuses. The present study was designed to investigate whether a reduction in sinus pressure would affect upper airway NO production. Thirteen healthy volunteers were investigated. A pressure chamber was used to lower the ambient pressure to -4.9 kPa. NO was sampled from one nostril or via a drainage tube inserted into the maxillary sinus before, during and after the hypobaric exposure. When the pressure was decreased, NO levels increased from 256 +/- 15 to 316 +/- 19 ppb (n = 13, p < 0.001). The NO levels remained elevated (282 +/- 21 ppb; p < 0.05) when measurements were repeated 20 min after leaving the chamber. The nasal airway resistance (V2tot) also increased as a result of the chamber session (from 16 +/- 2 degrees before to 21 +/- 3 degrees after; p < 0.05). An increase in NO levels was also found when the experiments were repeated with NO sampled directly from the maxillary sinus (225 +/- 6 before and 265 +/- 9 ppb after; n = 6, p < 0.001). For control purposes the nasal analyses were repeated again, this time under hyperbaric conditions (+ 4.9 kPa). This resulted in a slight decrease in the NO levels (from 273 +/- 22 to 241 +/- 17 ppb; n = 10, p < 0.001), but there was no change in the nasal airway resistance. We conclude that a reduction in sinus pressure, as seen in upper airway allergy or infection, may result in an increase in upper airway NO production.

Adult↗

PubMed2002

The paranasal sinuses as reservoirs for nitric oxide.

OBJECTIVE: Nitric oxide (NO) is an important mediator and inflammatory marker in human upper airways. Enzymes responsible for NO production have been demonstrated both in the nose and in the paranasal sinuses, but NO levels in the sinuses are reported to be several times higher than those in the nose. It has been postulated that the paranasal sinuses may be the primary sites for NO production in the upper respiratory tract. The present study was designed to compare the NO levels sampled from the nose with those found in the paranasal sinuses. MATERIAL AND METHODS: NO levels in the maxillary sinus and nose were determined using a continuous chemiluminescence measuring technique in seven healthy volunteers. RESULTS: When NO was sampled, via a drainage tube inserted into the maxillary sinus, a transient peak in NO level was recorded. The maximal NO level (5,761 +/- 1,513 ppb; n = 7) was reached within 10 s and was followed by the establishment of a lower steady-state level (304 +/- 51 ppb). When NO was continuously sampled from the nose a steady-state level, similar to that found in the sinus, was immediately established (313 +/- 52 ppb). CONCLUSION: The data presented confirm previous findings of extremely high NO levels in the paranasal sinuses and suggest that these cavities may also function as reservoirs for NO.

Adult↗

PubMed1991

Peptide-containing Neurons Projecting to the Tongue of the Rat: Retrograde Tracing and Immunocytochemistry.

The origin and neuropeptide content of nerve fibres in the rat circumvallate papilla was studied by retrograde tracing in combination with immunocytochemistry. An injection of the retrograde tracer True Blue into the circumvallate papilla resulted in the appearance of labelled nerve cell bodies in the superior cervical, the stellate, the thyroid, the nodose, the jugular, the petrosal, the otic, the trigeminal and the dorsal root ganglia at level C2. Most of the True Blue-labelled nerve cells in the superior cervical ganglia contained neuropeptide Y. The majority of labelled cell bodies in the thyroid ganglia contained vasoactive intestinal peptide. In the jugular and trigeminal ganglia, the majority of the labelled nerve cell bodies stored calcitonin gene-related peptide. A small number of neurons in the medial reticular formation of the central nervous system was labelled. Tracer injections deep into the tongue tissue beneath the circumvallate papilla gave rise to True Blue-labelled neurons in the hypoglossal nucleus.

Journal Article↗

PubMed1986

Peptide-containing nerve fibres in human extracranial tissue: a morphological basis for neuropeptide involvement in extracranial pain?

It has been suggested that a number of peptides may be involved in the transmission of pain. In order to evaluate the possible role of peptides in the development of headache, we have, in the present study, examined the presence of nerve fibres containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in human temporal and occipital tissues. In the skin, delicate VIP, SP and CGRP fibres occur beneath the epidermis, sometimes running into the folds of the dermal ridges. In deeper layers of the dermis, small blood vessels are occasionally surrounded by single nerve fibres containing NPY, VIP, SP and CGRP. Large temporal and occipital arteries are surrounded by a meshwork of such fibres. In addition, NPY and VIP fibres are seen around sweat glands and hair follicles. Smooth muscle bundles in the dermis are surrounded by VIP fibres, whereas the temporal muscle per se is devoid of such fibres.

Calcitonin Gene-Related Peptide↗