| 1. |
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| 2. |
- Giglio, Daniel, 1977, et al.
(författare)
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Altered muscarinic receptor subtype expression and functional responses in cyclophosphamide induced cystitis in rats.
- 2005
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Ingår i: Autonomic neuroscience : basic & clinical. - : Elsevier BV. - 1566-0702. ; 122:1-2, s. 9-20
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Tidskriftsartikel (refereegranskat)abstract
- In the in vitro study, it was investigated whether the expression of muscarinic receptors and cholinergic responses were altered in the situation of experimental cystitis. Rats were treated with cyclophosphamide intraperitoneally and the bladders were excised 36-100 h later. Immunohistochemistry and immunoblotting showed all subtypes of the muscarinic receptor (M1-M5) to be present in the specimens from inflamed urinary bladders and controls. In the cyclophosphamide-treated rats, the expression of muscarinic M5 receptors was increased by more than 40 times (p<0.01; n=8) both in the smooth muscle and the urothelium. Both the maximal contractile response to carbachol and to a high potassium concentration was approximately halved in cyclophosphamide-treated tissues, whereas the reduction was substantially greater in response to low carbachol concentrations (
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| 3. |
- Lundgren, Ove, 1937, et al.
(författare)
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Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2, s. 16295-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The maintenance of the intestinal epithelium is of great importance for the survival of the organism. A possible nervous control of epithelial cell renewal was studied in rats and mice. Methods: Mucosal afferent nerves were stimulated by exposing the intestinal mucosa to capsaicin (1.6 mM), which stimulates intestinal external axons. Epithelial cell renewal was investigated in the jejunum by measuring intestinal thymidine kinase (TK) activity, intestinal H-3-thymidine incorporation into DNA, and the number of crypt cells labeled with BrdU. The influence of the external gut innervation was minimized by severing the periarterial nerves. Principal Findings: Luminal capsaicin increased all the studied variables, an effect nervously mediated to judge from inhibitory effects on TK activity or H-3-thymidine incorporation into DNA by exposing the mucosa to lidocaine (a local anesthetic) or by giving four different neurotransmitter receptor antagonists i.v. (muscarinic, nicotinic, neurokinin1 (NK1) or calcitonin gene related peptide (CGRP) receptors). After degeneration of the intestinal external nerves capsaicin did not increase TK activity, suggesting the involvement of an axon reflex. Intra-arterial infusion of Substance P (SP) or CGRP increased intestinal TK activity, a response abolished by muscarinic receptor blockade. Immunohistochemistry suggested presence of M3 and M5 muscarinic receptors on the intestinal stem/progenitor cells. We propose that the stem/progenitor cells are controlled by cholinergic nerves, which, in turn, are influenced by mucosal afferent neuron(s) releasing acetylcholine and/or SP and/or CGRP. In mice lacking the capsaicin receptor, thymidine incorporation into DNA and number of crypt cells labeled with BrdU was lower than in wild type animals suggesting that nerves are important also in the absence of luminal capsaicin, a conclusion also supported by the observation that atropine lowered thymidine incorporation into DNA by 60% in control rat segments. Conclusion: Enteric nerves are of importance in maintaining the intestinal epithelial barrier.
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| 4. |
- Nilsson, R. Henrik, 1976, et al.
(författare)
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Improving ITS sequence data for identification of plant pathogenic fungi
- 2014
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Ingår i: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 67:1, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- Plant pathogenic fungi are a large and diverse assemblage of eukaryotes with substantial impacts on natural ecosystems and human endeavours. These taxa often have complex and poorly understood life cycles, lack observable, discriminatory morphological characters, and may not be amenable to in vitro culturing. As a result, species identification is frequently difficult. Molecular (DNA sequence) data have emerged as crucial information for the taxonomic identification of plant pathogenic fungi, with the nuclear ribosomal internal transcribed spacer (ITS) region being the most popular marker. However, international nucleotide sequence databases are accumulating numerous sequences of compromised or low-resolution taxonomic annotations and substandard technical quality, making their use in the molecular identification of plant pathogenic fungi problematic. Here we report on a concerted effort to identify high-quality reference sequences for various plant pathogenic fungi and to re-annotate incorrectly or insufficiently annotated public ITS sequences from these fungal lineages. A third objective was to enrich the sequences with geographical and ecological metadata. The results – a total of 31,954 changes – are incorporated in and made available through the UNITE database for molecular identification of fungi (http://unite.ut.ee), including standalone FASTA files of sequence data for local BLAST searches, use in the next-generation sequencing analysis platforms QIIME and mothur, and related applications. The present initiative is just a beginning to cover the wide spectrum of plant pathogenic fungi, and we invite all researchers with pertinent expertise to join the annotation effort.
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| 5. |
- Ryberg, Anders, 1978, et al.
(författare)
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Characterization of PrejunctionalMuscarinic Receptors: Effects on the Release of VIP and Functional Responses and Receptor Expression in the Ovine Submandibular Gland
- 2009
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Ingår i: Advances In Pharmacological Sciences. - : Hindawi Limited. - 1687-6334 .- 1687-6342. ; 2009, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- In the in vivo experiments on anaesthetized sheep, it was presently examined whether muscarinic receptor antagonists with diverse selectivity affect the release of VIP in response to electrical stimulation of the parasympathetic chorda tympanic nerve differently, and if the changes in the release could be associated to altered secretory and vasodilator responses. The location of the muscarinic receptor subtypes was examined also. In the experiments, blood was collected out of the submandibular venous drainage before and during electrical stimulation of chorda tympani nerve in the absence and presence either of pirenzepine or methoctramine. While metchoctramine increased the output of protein, pirenzepine inhibited flow of saliva and increased protein output, vasodilatation, and VIP output. In morphological examinations, the inhibitory muscarinic M4 receptor occurred interacinarily in the gland. It is concluded that prejunctional muscarinic receptors, most likely of theM4 subtype, exert inhibitory modulation of the parasympathetic release of VIP in the ovine submandibular gland.
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| 6. |
- Ryberg, Anders, 1978, et al.
(författare)
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Cholinergic submandibular effects and muscarinic receptor expression in blood vessels of the rat.
- 2008
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Ingår i: Archives of oral biology. - : Elsevier BV. - 0003-9969. ; 53:7, s. 605-16
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Tidskriftsartikel (refereegranskat)abstract
- In order to functionally characterise the muscarinic vasodilator responses, effects of cholinergic agonists were studied on isolated preparations of the rat submandibular artery and vein and carotid and jugular vessels. Tentatively, a cholinergic regulatory mechanism having different effects on the arterial and venous vessels would enhance vascular fluid recruitment for the secretory response. In vitro functional findings were correlated to the expression and cellular location of the different receptors that were assessed by immunohistochemistry. In order to find in vivo correlates to the in vitro findings, the influence of muscarinic receptors on permeability was studied on the vasculature of the submandibular gland in anaesthetised rats. Staining for muscarinic M1 receptors occurred in the endothelium, and muscarinic M5 receptors, and possibly M3 also, were detected in the arterial smooth muscle. In venous endothelium, muscarinic M1 and M4 receptors occurred. In the jugular smooth muscle layer, staining for M1, and possibly also for M3, appeared. Muscarinic agonists caused arteries to relax and veins to contract. The nitric oxide synthase inhibitor Nomega-nitro-l-arginine (l-NNA; 10(-4)M) markedly reduced the cholinergic-evoked relaxation of pre-contracted carotid arterial preparations. In the presence of 4-DAMP (10(-7)M), the relaxation to cholinergic agonists was inhibited. Pirenzepine (10(-5)M) did not only inhibit the relaxatory effects, but even reversed the effects, while it in the jugular vein abolished the cholinergic effects. The arterial nitric oxide-dependent response to muscarinic receptor stimulation consisted of two parts-one sensitive to pirenzepine and 4-DAMP and the other to 4-DAMP only. Inhibition of the former part only, resulted in cholinergic arterial contraction. Also, the submandibular artery and vein responses to muscarinic receptor stimulation show a resemblance with those of the carotid and jugular vessels, i.e. a pronounced arterial relaxation and a contractile component in the venous response. In vivo examination of submandibular glandular vasculature by studying glandular permeability to Evans blue, confirmed the in vitro observations indicating muscarinic M1 receptors preserving perfusion pressure during the secretory process.
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| 7. |
- Ryberg, Anders, 1978, et al.
(författare)
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Expression of muscarinic receptor subtypes in salivary glands of rats, sheep and man.
- 2008
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Ingår i: Archives of Oral Biology. - : Elsevier BV. - 0003-9969 .- 1879-1506. ; 53:1, s. 66-74
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Tidskriftsartikel (refereegranskat)abstract
- In rat parotid, submandibular and sublingual glands and in ovine parotid and in human labial glands, the expression of muscarinic receptor subtypes was examined by immunoblotting and immunohistochemistry. Functional correlates were searched for in rat salivary glands. In the rat submandibular and sublingual glandular tissues clear signals of muscarinic M1 and M5 receptors could be detected in the immunoblotting and vague bands for muscarinic M3 and, in particular for, M4 receptors. The rat parotid gland differed. In this gland, the signal was less obvious for the muscarinic M1 receptor, and further, muscarinic M4 receptors appeared more strongly marked than in the submandibular glands. The results from the immunohistochemistry could be interpreted as the muscarinic M4 receptors are located on nerve fibres, since the outer layer of lobuli were densely stained. Intraglandular vessels in the rat submandibular and parotid glands showed expression of M3 receptors. In contrast to the parotid gland, the submandibular vessels also expressed M1 and M2 receptors. Occasionally M5 receptors appeared in the arteries and veins also. The functional studies in the rat confirmed muscarinic M1 receptor mediated secretion in the submandibular gland. Since the M1 receptor blockade did not affect submandibular blood flow, indirect vascular effects could not in total explain the secretory inhibition. Also in the human labial glands, muscarinic M1, M3 and M5 receptors occurred. No or low amounts of muscarinic M2 and M4 receptors could be detected. In patients with Sjögren-like symptoms an up-regulation of M3, M4 and M5 receptors was apparent in the labial glands. In ovine parotid glands all receptors could be detected, but constantly with vague bands for muscarinic M2 receptors. In conclusion, muscarinic M1 receptors seem to be expressed in seromucous/mucous glands. A secretory effect by muscarinic M5 receptors is not to be excluded, since they were expressed in all the glands examined. However, other functions, such as promotion of inflammation, cell growth and proliferation are possible as well.
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| 8. |
- Ryberg, Anders, 1978
(författare)
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On the Autonomic Control of Blood Flow and Secretion in Salivary Glands. Functional and morphological aspects on muscarinic receptor subtypes in different species.
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parasympathetic nervous activity is the principal stimulus for evoking fluid responses within salivary glands. Concomitantly to the onset of this response, the blood flow increases. The responses, in particular the vasodilatation, consist of an atropine-sensitive acetylcholine-mediated part and an atropine-resistant part mediated via non-adrenergic, non-cholinergic (NANC) transmitters. It has been generally agreed that the cholinergic effects are mediated by muscarinic M3 receptors. However, this view has been questioned, since most muscarinic receptors are expressed and muscarinic M1 receptors elicit functional effects in salivary glands. The distribution and function of the muscarinic receptors is not unravelled, neither according to secretion nor vasodilatation. The aim of this thesis has been to investigate the roles of different muscarinic subtypes in the control of blood flow and secretion in salivary glands. In the thesis, the expression of muscarinic receptors in salivary glands and related blood vessels was investigated using immunoblotting and/or immunohistochemistry. Furthermore the effects of muscarinic stimulation and blockade were investigated on isolated vessels, on the secretion of saliva, on glandular blood flow and vessel permeability. The thesis includes observations on rats, sheep and man. It is shown that M1 receptors contribute considerably, in addition to the functionally most significant M3 receptor, to the fluid secretory responses of rats and sheep. The M1 receptor is particularly apparent in seromucous and mucous glands, and of particular functional significance at low intense stimulation. Since the occurrence pattern was the same in human salivary glands, M1 receptors may be of significance in man also. Notably, in the human glands, inflammation increased the expression of muscarinic M5 receptors. In the arterial blood vessels muscarinic M1 receptors generally occurred in the endothelium, and muscarinic M5 receptors, and possibly M3 also, were detected in the smooth muscle. In venous endothelium muscarinic M1 and M4 receptors occurred, while M1 and/or M3 were expressed in the smooth muscle layer. Cholinergic stimulation generally caused arterial vasodilatation, which was mainly dependent on nitric oxide. The response was mediated by muscarinic M1 and possibly M5 receptors, in addition to the M3 receptor. The venous response included a contractile M1 mediated component that may preserve perfusion pressure during the secretory process. In tissue in close vicinity to the parenchymal tissues, M1 and in particular M4 receptors occurred. In the sheep, the increase of submandibular secretory and vasodilator responses to electrical stimulation of the parasympathetic nerve in the presence of muscarinic antagonists were explained by neuronal muscarinic M4 receptors. These receptors inhibited the release of transmitters as was shown for the NANC transmitter VIP. The role of muscarinic M5 receptors is unclear but may affect on the vascular response or more likely to be correlated to inflammation. In general, the expression pattern and functions of the muscarinic receptors subtypes showed resemblance in the examined species. All muscarinic receptors occur in the salivary glands. In seromucous/mucous glands, muscarinic M1 receptors contribute substantially to the secretory response. In the vasculature, the muscarinic receptor subtypes interact, possibly via autocrine mechanisms, for preserving the hemodynamics in the glands.
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| 9. |
- Tobin, Gunnar, 1954, et al.
(författare)
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Distribution and function of muscarinic receptor subtypes in the ovine submandibular gland.
- 2006
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 100:4, s. 1215-23
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Tidskriftsartikel (refereegranskat)abstract
- The effects of muscarinic receptor antagonists on responses to electrical stimulation of the chorda-lingual nerve were determined in pentobarbitone-anesthetized sheep and correlated to the morphology of tissue specimens. Stimulation at 2 Hz continuously, or in bursts of 1 s at 20 Hz every 10 s, for 10 min induced similar submandibular fluid responses (19 +/- 3 vs. 21 +/- 3 microl x min(-1) x g gland(-1)), whereas vasodilatation was greater during stimulation in bursts (-52 +/- 4 vs. -43 +/- 5%; P < 0.01). Continuous stimulation at 8 Hz induced substantially greater responses (66 +/- 9 microl x min(-1) x g gland(-1) and -77 +/- 3%). While atropine (0.5 mg/kg iv) abolished the secretory response at 2 and 20 Hz (1:10 s), a small response persisted at 8 Hz (<5%). The "M1-selective" antagonist pirenzepine (40 microg/kg iv) reduced the fluid response at all frequencies tested (P < 0.05-0.01), most conspicuously at 2 Hz (reduced by 69%). Methoctramine ("M2/M4-selective"; 100 microg/kg iv; n = 5) had no effect on fluid or the vascular responses but increased the protein output at 2 (+90%, P < 0.05) and 8 Hz (+45%, P < 0.05). The immunoblotting showed distinct bands for muscarinic M1, M3, M4, and M5 receptors, and immunohistochemistry showed muscarinic M1 and M3 receptors to occur in the parenchyma. Thus muscarinic M1 receptors contribute to the secretory response to parasympathetic stimulation but have little effect on the vasodilatation in the ovine submandibular gland. Increased transmitter release caused by blockade of neuronal inhibitory receptors of the M4 subtype would explain the increase in protein output.
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