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Biomedical subjects

R Uddman

Publications and source records attributed to R Uddman.

At least 37 records · Page 2Linked to original sources

The human superior cervical ganglion: neuropeptides and peptide receptors.

Noradrenaline (NA)- and neuropeptide Y (NPY)-containing cell bodies were found to occur in high numbers (>75% of all cells were positive) in the human superior cervical ganglion and distributed homogeneously throughout the ganglion and showed colocalisation. A few cell bodies were VIP-immunoreactive (-ir) (less than 5%) but none of them showed NOS-, CGRP- or SP-ir. Receptor mRNA expression was studied with RT-PCR. Total RNA from the superior cervical ganglion was successfully extracted. By using appropriate sense and antisense oligonucleotides designed from the published human sequences, we could show the presence of mRNA for the human NPY Y1, NPY Y2 and VPAC1 receptors but not CGRP1 receptor mRNA.

Aged↗

Altered ratio of endothelin ET(A)- and ET(B) receptor mRNA in bronchial biopsies from patients with asthma and chronic airway obstruction.

Using a reverse transcription-polymerase chain reaction (RT-PCR) based assay the ratio of mRNA for the human endothelin ET(A) and ET(B) receptors in bronchial biopsies was assessed. In patients with diagnoses like bronchial cancer, endothelin ET(A) mRNA was the dominating subtype (ratio 3.74 +/- 0.99). Subjects with the diagnosis of asthma or chronic obstructive pulmonary disease showed significantly higher levels (ratio 0.81 +/- 0.04) of endothelin ET(B) receptor mRNA compared to endothelin ET(A) receptor mRNA. Our results indicate alterations in the endothelin receptor balance in these states.

Aged↗

Expression of calcitonin gene-related peptide-1 receptor mRNA in human tooth pulp and trigeminal ganglion.

Numerous nerve fibres containing calcitonin gene-related peptide (CGRP) were found by immunocytochemistry in human molar pulp. These nerves were often seen around small blood vessels and as free endings without vascular contact. In the trigeminal ganglion a large number of CGRP-immunoreactive nerve-cell bodies, mostly of small to medium size, was encountered. Reverse transcriptase-polymerase chain reaction, using specific sense and antisense primers, detected mRNA expression of the human CGRP1 receptor in the pulp tissue and the trigeminal ganglion. Thus, both CGRP-containing nerve fibres and CGRP1 receptor mRNA are present in human tooth pulp, where they may be involved in the regulation of vascular tone and other local reactions to injury.

Adult↗

Expression of endothelin A- and B-receptors in human nasal mucosa.

Several studies have suggested an important role for the endothelin (ET) family of peptides in the vascular regulation of the nose. In addition, there is increasing evidence that ETs play a role in allergic airway inflammation. Endothelin is produced locally in the nose and mediates its effects via two distinct receptor subtypes, termed ET(A) and ET(B). Using reverse transcriptase-polymerase chain reaction, mRNAs encoding ET(A)- and ET(B)-receptors were detected in the human lower turbinate and sinus mucosa. The possibility of local release of ETs in connection with specific target receptors suggests a role for endothelin in the regulation of vascular tone, glandular secretion and epithelial functions.

Adult↗

Expression of histamine H1 and H2 receptors in human nasal mucosa.

mRNA encoding histamine H1 and H2 receptors were detected in the human nasal mucosa using reverse transcriptase-polymerase chain reaction. The possibility of local release in connection with specific target receptors suggests a role for histamine in the regulation of vascular tone, glandular secretion and epithelial functions.

Adult↗

Helospectin-like peptides: immunochemical localization and effects on isolated cerebral arteries and on local cerebral blood flow in the cat.

Helospectin I and II and helodermin are nonamidated, vasoactive intestinal peptide (VIP)-like peptides, isolated from the salivary gland venom of the lizards Heloderma suspectum and Heloderma horridum. Helospectin I has 38 amino acid residues and differs from helospectin II in that it has an additional serine residue at the C-terminus. Numerous nerve fibers containing helospectin-like immunoreactivity (LI) and a few fibers containing helodermin-LI were present in the adventitia and at the adventitia-media border of cat cerebral arteries. In the sphenopalatine ganglion, numerous nerve cell bodies containing helospectin-LI were seen. Double immunostaining revealed that helospectin-LI nerve cell bodies coexisted with VIP-containing cell bodies. Radioimmunoassay showed high levels of helospectin-LI in extracts of cerebral vessels from the circle of Willis (27.4 pg/mg [wt/wt]). Helospectin I and II and helodermin (10(-10) to 10(-6) mol/L) produced concentration-dependent relaxations of feline middle cerebral arteries amounting to 50% to 80% of precontraction induced by U46619. The maximum effects and the potency were similar to that of VIP. Neither of these peptides elicited endothelium-dependent relaxations. Intracerebral microinjection of helospectin and helodermin produced a moderate concentration-dependent increase of the cerebral blood flow of alpha-chloralose anesthetized cats. The maximum increase (21 +/- 5%) was observed after the injection of 5 microg helodermin, whereas 16 +/- 7% was seen with helospectin I and 19 + 5% with helospectin II. The results suggest that helospectin/helodermin-like peptides co-localize with VIP in perivascular nerve fibers originating in the sphenopalatine ganglion. They seem to have strong and potent vasodilator effects.

Animals↗

Expression of NPY Y1 and CGRP1 receptors in human nasal mucosa: implications in allergic rhinitis.

Numerous nerve fibers containing neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) have been found in the human nasal mucosa by means of immunocytochemistry. We detected NPY Y1 and CGRP1 receptors at the same location using reverse transcriptase-polymerase chain reaction. The possibility of local release in connection with specific target receptors suggests a role for endogenous NPY and CGRP in the regulation of vascular tone, glandular secretion, and epithelial functions.

Adult↗

Calcitonin gene-related peptide and nitric oxide in the trigeminal ganglion: cerebral vasodilatation from trigeminal nerve stimulation involves mainly calcitonin gene-related peptide.

Nitric oxide (NO) is a novel neurotransmitter candidate to which a large number of physiological roles has been ascribed. In the present study, immunocytochemistry was used to demonstrate NO synthase (NOS) and to investigate possible co-localization with other neurotransmitters. In the trigeminal ganglion of the cat, a moderate number of NOS immunoreactive nerve cell bodies was seen, of which the major part also expressed calcitonin gene-related peptide (CGRP). The nerve cell bodies expressing NOS in the trigeminal ganglion were predominantly of small to medium size; while numerous cell bodies of varying size contained CGRP. With in situ hybridization using oligonucleotide probes, CGRP mRNA was demonstrated in almost all trigeminal neurons of the cat. Stimulation of the nasociliary nerve resulted in a frequency-dependent increase in ipsilateral local cortical blood flow by 30 +/- 6%. Administration of the NOS inhibitor NG-nitro-L-arginine-methylester (L-NAME) did not significantly alter this response when applied intravenously or on the cortical surface. Local cortical administration of the CGRP blocker h-CGRP (8-37) did not alter the cerebral vasodilator response to hypercapnia or resting flow. However, the nasociliary nerve response was reduced by 50% after h-CGRP (8-37), with a general shift to the right of the frequency-response curve. These data suggest that although NOS is seen in several trigeminal ganglion cells and coexists with CGRP in a subpopulation of the sensory neurons, its role in trigeminally mediated vasodilatation was not significant.

Animals↗

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↗

Localization of neuropeptide Y Y1 receptor mRNA in human tooth pulp.

With immunocytochemistry numerous nerve fibres containing neuropeptide Y (NPY) were found in human molar pulp tissue, often around small blood vessels. Reverse transcriptase-polymerase chain reaction, using specific primers, detected mRNA of the human NPY Y1 receptor in the human pulp tissue. Thus, both NPY-containing nerve fibres and NPY Y1 receptor mRNA are present in human tooth pulp, possibly regulating vascular tone and pain perception.

Adult↗

Nitric oxide is a regulator of mucociliary activity in the upper respiratory tract.

The in vitro effects of the nitric oxide (NO) substrate L-arginine on ciliary beat frequency and the in vivo effects of the NO donor sodium nitroprusside (SNP) on mucociliary activity were investigated in the rabbit maxillary sinus mucosa with photoelectric techniques. L-Arginine increased ciliary beat frequency in vitro with a maximum response of 27.1% +/- 6.4% at 10(-3) mol/L, and this effect was reversibly blocked by pretreatment with the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine, whereas D-arginine had no such effect. SNP increased mucociliary activity in vivo, the peak response of 36.8% +/- 4.2% being obtained at the dose of 30.0 microg/kg. No tachyphylaxis was observed after repeat challenge with SNP. The increase in mucociliary activity caused by SNP was largely unaffected by pretreatment with the calcium channel blocker nifedipine, the cyclooxygenase inhibitor diclofenac, and the cholinergic antagonist atropine. The nonselective beta-blocker propranolol delayed the peak response of SNP to 7 to 8 minutes after challenge, compared with 1 to 2 minutes after challenge in animals without pretreatment. The results show the NO substrate L-arginine and the NO donor SNP to have ciliostimulatory effects in vitro and in vivo, respectively. The occurrence of NOS production in the sphenopalatine ganglion and sinus mucosa of the rabbit was studied by immunohistochemistry for NOS activity or nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry. The latter is an indirect sign of neuronal NOS activity. Numerous NOS-containing cell bodies were seen in the sphenopalatine ganglion; in the sinus mucosa a moderate supply of thin NOS-immunoreactive nerve fibers was seen. Taken together, the morphologic findings and the functional results indicate NO to be a regulator of mucociliary activity in upper airways.

Animals↗

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↗

Expression of calcitonin gene-related peptide1 receptor mRNA in human trigeminal ganglia and cerebral arteries.

Reverse transcriptase polymerase chain reaction (RT-PCR) using primers for the recently cloned human CGRP1 receptor detected mRNA expression of CGRP1 receptors in trigeminal ganglia and cerebral vessels, obtained at autopsy or during neurosurgical tumor resections. An RT-PCR product of the expected size (339 bp) was seen in cerebral arteries, both in the presence and in the absence of endothelium and in trigeminal ganglia. Sequence analysis of the RT-PCR product of the published sequence showed 100% homology with the human CGRP1 receptor. The presence of the CGRP1 receptor mRNA in human trigeminal ganglia and cerebral blood vessels, indicates the occurrence of both prejunctional (trigeminal) and postjunctional location (blood vessels) of the CGRP1 receptor.

Antisense Elements (Genetics)↗

The induction of nitric oxide-mediated relaxation of human isolated pulmonary arteries by PACAP.

1. The effects of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) were analysed in human isolated circular segments of pulmonary arteries. Guinea-pig pulmonary arteries were used for comparison. The responses obtained were analysed in relation to the vascular endothelium and the nitric oxide (NO) synthase inhibitor NG-monomethyl L-arginine (L-NMMA). 2. PACAP and VIP induced concentration-dependent relaxations of precontracted pulmonary arteries. The maximal dilator response (Imax, %) and the potency (pEC50 value) were the same for both peptides, and there were no differences in the effects obtained on human and guinea-pig segments. PACAP and VIP were both more potent that acetylcholine (ACh). 3. Removal of the vascular endothelium abolished the PACAP induced dilator response in pulmonary arteries from both species. The VIP induced dilatation was unaffected, whereas the response to ACh was abolished. L-NMMA given before PACAP inhibited the dilatation. Furthermore, L-NMMA also reversed the dilatation already induced by PACAP and excess concentrations of L-arginine restored the dilator response of the L-NMMA treated arteries. 4. PACAP is a potent dilator of human pulmonary arteries. Although the dilator effect seems to be similar in amplitude to the one induced by VIP, the present results suggest differences in the underlying mechanisms of action (endothelium-dependency) between the two peptides.

Acetylcholine↗

Pituitary adenylate cyclase activating polypeptide and nitric oxide synthase are expressed in the rat ciliary ganglion.

AIMS: To study the distribution in the rat ciliary ganglion of neurons synthesising and storing the recently discovered neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) and neuronal nitric oxide synthase (NOS), the neuronal marker of the novel gaseous transmitter nitric oxide. METHODS: Neurons expressing PACAP and neuronal NOS mRNA were identified in the rat ciliary ganglion by in situ hybridisation with radiolabelled oligonucleotide probes. Immunocytochemistry was used to demonstrate immunoreactive neuropeptides and NOS. RESULTS: Immunocytochemistry demonstrated immunoreactivity for PACAP and NOS in a small number of neuronal cell bodies. In situ hybridisation revealed that NOS and PACAP were expressed in numerous ganglion cell somata. The well established ciliary messengers vasoactive intestinal peptide and neuropeptide Y were found in a large number of neuronal cell bodies. CONCLUSION: These results demonstrate that PACAP and NOS are synthesised and stored in the ciliary ganglion. These findings further illustrate the mixed nature of the ciliary ganglion and may provide a basis for the understanding of the diverse physiological functions of this ganglion.

Animals↗

Reduced nasal airway resistance following uvulopalatoplasty.

Active anterior rhinomanometry was performed on adult healthy snorers before and after uvulopalatopharyngoplasty or laser uvulopalatoplasty. Significant reduction of the nasal airway resistance both before and after pharmacological decongestion of the nasal mucosa was found in a group of 46 patients. Oedema disappearing after surgery may be an explanation for the results.

Adult↗

Cerebral vasodilatation in the cat involves nitric oxide from parasympathetic nerves.

The recent description of the synthesis of nitric oxide (NO) in vivo and its putative role in endothelial-dependent vasodilatation has led to considerable interest in possible roles for the molecule. In this study the distribution, origin and some aspects of the physiology of NO found in the cerebral circulation is examined. A rich supply of nerve fibres displaying immunoreactivity against nitric oxide synthase (NOS) could be seen in the adventitia of the cat cerebral vessels. There was a large number of NOS-positive cells in the sphenopalatine ganglion and these constituted a sub-population of the vasoactive intestinal polypeptide (VIP) positive cells. Blockade of NOS activity with NG-nitro-L-arginine methyl ester (L-NAME) significantly attenuated the cerebral vasodilator response to facial nerve stimulation when applied locally to the cortex. Intravenous administration of L-NAME did not affect the VII-elicited cerebral vasodilator response. It may be concluded that the parasympathetic nerves innervating the cerebral circulation contain NOS and furthermore, since blockade of NOS reduces parasympathetic vasodilatation, that NO is one of the transmitters in this system.

Animals↗