| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- Soukup, Ondrej, et al.
(författare)
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Methylacridinium and its cholinergic properties.
- 2009
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Ingår i: Neurotoxicity research. - : Springer Science and Business Media LLC. - 1029-8428 .- 1476-3524. ; 16:4, s. 372-7
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Tidskriftsartikel (refereegranskat)abstract
- 10-Methylacridinium iodide (methylacridinium; MA) is an inhibitor of cholinesterases. Inhibitors of acetylcholinesterase (AChE) are used in the treatment of myasthenia gravis, Alzheimer's disease, and in the prophylaxis of poisoning with organophosphates. Using spectrophotometric Ellman's method at 436 nm and commercial enzymes we found that MA inhibits AChE by binding with relatively high potency to the peripheral anionic site (IC(50) = 1.68 +/- 0.14 muM; human recombinant AChE) and equally to its inhibition of butyrylcholinesterase (BuChE; IC(50) = 3.54 +/- 0.27 muM; BuChE from human serum). MA also inhibits the binding of [(3)H]N-methylscopolamine to the muscarinic M2 receptor subtype, possibly in an allosteric manner (IC(50) = 1.90 muM). Functional effects on both the enzyme and the receptor could be observed in contractile studies on the isolated rat bladder. The ability of MA to cross the blood-brain barrier (log P = -0.32; polar surface area 3.88) provides prerequisites for a potential use of the drug in the treatment of neural disorders.
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| 5. |
- Soukup, Ondrej, et al.
(författare)
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The effect of H1-6 on cholinesterases and on the cholinergic system of the rat bladder
- 2009
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Ingår i: TOXICOLOGY LETTERS. - 0378-4274. ; 189:Sp Iss SI
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Konferensbidrag (refereegranskat)abstract
- The current standard treatment of organophosphate poisoning consists of an administration of anticholinergic drugs and cholinesterase reactivators (oximes). Oximes can react – except their reactivating effect on cholinesterases – directly with cholinoreceptors. HI-6 is an oxime that may have an inhibitory effect on the muscarinic receptors, too. In our work, we have investigated an influence of HI-6 on the acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and on the muscarinic receptors in vitro. The study was conducted using biosensor technique and on the rat bladder using in vitro test (tissue bath; methacholine as muscarinic agonist). IC50 for BChE from human serum was determined to be 1.01 × 10−6 M and for human erythrocytes AChE 3.31 × 10−6 M, respectively. We assume that the demonstrated contractile response can be attributed to the inhibition of the AChE at the lower concentration and to a predominant inhibition of muscarinic receptor at higher concentration of compound tested.
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| 6. |
- Soukup, Ondrej, et al.
(författare)
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The effect of HI-6 on cholinesterases and on the cholinergic system of the rat bladder.
- 2008
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Ingår i: Neuro endocrinology letters. - 0172-780X. ; 29:5, s. 759-62
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The current standard treatment of organophosphate poisoning consists of an administration of anticholinergic drugs and cholinesterase reactivators (oximes). Oximes can react - except their reactivating effect on cholinesterases - directly with cholinoreceptors. HI-6 is an oxime that may have an inhibitory effect on the muscarinic receptors, too. METHODS: In our work, we have investigated an influence of HI-6 on the acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and on the muscarinic receptors in vitro. The study was conducted using biosensor technique and on the rat bladder using in vitro test (tissue bath; methacholine as muscarinic agonist). IC50 for BChE from human serum was determined to be 1.01x10-6 M and for human erythrocytes AChE 3.31x10-6 M, respectively. CONCLUSION: We assume that the demonstrated contractile response can be attributed to the inhibition of the AChE at the lower concentration and to a predominant inhibition of muscarinic receptor at higher concentration of compound tested.
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