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- 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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| 3. |
- Andersson, Michael, 1980, et al.
(författare)
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Cholinergic nitric oxide release from the urinary bladder mucosa in cyclophosphamide-induced cystitis of the anaesthetized rat.
- 2008
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Ingår i: British journal of pharmacology. - : Wiley. - 0007-1188. ; 153:7, s. 1438-44
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Previous reports have suggested that nitric oxide (NO) may be released by cholinergic stimuli in the rat bladder in cyclophosphamide-induced cystitis, affecting bladder function. In the current study, we evaluated the effects of cyclophosphamide-induced cystitis on muscarinic whole bladder contractile responses in vivo, and further, if NO might be released from the mucosa by cholinergic stimuli.Experimental approach: Male rats were pre-treated either with cyclophosphamide (100 mg kg(-1); to induce cystitis) or saline (serving as controls). 60 h later, rats were anaesthetized and bladder pressure monitored.Key results: The muscarinic receptor agonist methacholine (MeCh; 0.5-5 mug kg(-1) i.v.) induced similar contractions (i.e. bladder pressure increases) in inflamed bladders as in controls, which were attenuated dose-dependently by the muscarinic M(1)/M(3)/M(5) antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 0.1-1000 mug kg(-1) i.v.). In inflamed bladders, the cholinergic bladder contractions were enhanced after removing the mucosa, while cholinergic contractions were similar in intact and urothelium-denuded inflamed bladders in the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 30 mg kg(-1) i.v.). L-NAME attenuated the antagonistic effect of 4-DAMP on MeCh-induced contractions in intact inflamed bladders. However L-NAME did not affect the antagonism by 4-DAMP of MeCh-induced contractions of urothelium-denuded bladders, under control conditions or with cyclophosphamide-induced cystitis.Conclusions and implications: In cyclophosphamide-induced cystitis, the cholinergic function of the bladder is altered. In the inflamed bladder, NO seems to be released via cholinergic stimuli through mucosal muscarinic M(3)/M(5) receptors, presumably on urothelial cells, affecting bladder function.British Journal of Pharmacology (2008) 153, 1438-1444; doi:10.1038/bjp.2008.6; published online 4 February 2008.
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| 8. |
- Andersson, Michael, 1980, et al.
(författare)
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Muscarinic receptor subtypes involved in urothelium-derived relaxatory effects in the inflamed rat urinary bladder.
- 2012
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Ingår i: Autonomic neuroscience : basic & clinical. - : Elsevier BV. - 1872-7484. ; 170:1-2, s. 5-11
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Tidskriftsartikel (refereegranskat)abstract
- Functional studies have shown altered cholinergic mechanisms in the inflamed bladder, which partly depend on muscarinic receptor-induced release of nitric oxide (NO). The current study aimed to characterize which muscarinic receptor subtypes that are involved in the regulation of the nitrergic effects in the bladder cholinergic response during cystitis. For this purpose, in vitro examinations of carbachol-evoked contractions of inflamed and normal bladder preparations were performed. The effects of antagonists with different selectivity for the receptor subtypes were assessed on intact and urothelium-denuded bladder preparations. In preparations from cyclophosphamide (CYP; in order to induce cystitis) pre-treated rats, the response to carbachol was about 75% of that of normal preparations. Removal of the urothelium or administration of a nitric oxide synthase inhibitor re-established the responses in the inflamed preparations. Administration of 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) inhibited the carbachol-induced contractile responses of preparations from CYP pre-treated rats less potently than controls. Pirenzepine and p-fluoro-hexahydro-sila-diphenidol (pFHHSiD) affected the carbachol-induced contractile responses to similar extents in preparations of CYP pre-treated and control rats. However, the Schild slopes for the three antagonists were all significantly different from unity in the preparations from CYP pre-treated rats. Again, l-NNA or removal of the urothelium eliminated any difference compared to normal preparations. This study confirms that muscarinic receptor stimulation in the inflamed rat urinary bladder induces urothelial release of NO, which counteracts detrusor contraction.
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| 10. |
- Andersson, Michael, 1980, et al.
(författare)
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Pharmacological modulation of the micturition pattern in normal and cyclophosphamide pre-treated conscious rats.
- 2011
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Ingår i: Autonomic neuroscience : basic & clinical. - : Elsevier BV. - 1872-7484. ; 159:1-2, s. 77-83
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Tidskriftsartikel (refereegranskat)abstract
- In the current study, we wanted to assess the influence of muscarinic receptors, nitric oxide and purinoceptors on the micturition pattern of conscious normal and cyclophosphamide (CYP) pre-treated rats. The micturition parameters were assessed using a metabolic cage. Rats were pre-treated with either saline or CYP, to induce cystitis, followed by treatment with either the muscarinic M1/M3/M5 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), the nitric oxide synthase blocker N(ω)-nitro-L-arginine methyl (L-NAME), the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) or a combination of 4-DAMP with PPADS or L-NAME. Voiding volumes per micturition event were significantly lower in CYP pre-treated than in saline pre-treated rats. Neither 4-DAMP nor L-NAME had any effect in the normal rats, whereas PPADS reduced the micturition volume per event. In CYP pre-treated rats, 4-DAMP and L-NAME significantly increased voiding volumes per event and micturition frequency, respectively. 4-DAMP dose-dependently reduced the differences in micturition activity between saline and CYP pre-treated rats. We show that cystitis changes the urodynamics in conscious rats and that this change seems to depend on the production of NO and on altered muscarinic receptor effects. The altered muscarinic receptor responses are likely to per se involve NO-mediated mechanisms.
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