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Cholinergic responses of ophthalmic arteries in M3 and M5 muscarinic acetylcholine receptor knockout mice.

ABSTRACT: PURPOSE:To determine the functional role of M(3) and M(5) muscarinic acetylcholine receptor subtypes in ophthalmic arteries using gene-targeted mice. METHODS:Muscarinic receptor gene expression was quantified in murine ophthalmic arteries using real-time PCR. To test the functional relevance of M(3) and M(5) receptors, ophthalmic arteries from mice deficient in either subtype (M3R(-/-), M5R(-/-), respectively) and wild-type controls were isolated, cannulated with micropipettes, and pressurized. Changes in luminal vessel diameter in response to muscarinic and nonmuscarinic receptor agonists were measured by video microscopy. RESULTS:With the use of real-time PCR, all five muscarinic receptor subtypes were detected in ophthalmic arteries. However, mRNA levels of M(1), M(3), and M(5) receptors were higher than those of M(2) and M(4) receptors. In functional studies, after preconstriction with phenylephrine, acetylcholine and carbachol produced concentration-dependent dilations of ophthalmic arteries that were similar in M5R(-/-) and wild-type mice. Strikingly, cholinergic dilation of ophthalmic arteries was almost completely abolished in M3R(-/-) mice. Deletion of either M(3) or M(5) receptor did not affect responses to nonmuscarinic vasodilators such as bradykinin or nitroprusside. CONCLUSIONS:These findings provide the first evidence that M(3) receptors are critically involved in cholinergic regulation of diameter in murine ophthalmic arteries.

SUBMITTER: Gericke A

PROVIDER: S-EPMC4111104 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Cholinergic responses of ophthalmic arteries in M3 and M5 muscarinic acetylcholine receptor knockout mice.

Gericke Adrian A Mayer Veronique G A VG Steege Andreas A Patzak Andreas A Neumann Ulrike U Grus Franz H FH Joachim Stephanie C SC Choritz Lars L Wess Jürgen J Pfeiffer Norbert N

Investigative ophthalmology & visual science 20090430 10

<h4>Purpose</h4>To determine the functional role of M(3) and M(5) muscarinic acetylcholine receptor subtypes in ophthalmic arteries using gene-targeted mice.<h4>Methods</h4>Muscarinic receptor gene expression was quantified in murine ophthalmic arteries using real-time PCR. To test the functional relevance of M(3) and M(5) receptors, ophthalmic arteries from mice deficient in either subtype (M3R(-/-), M5R(-/-), respectively) and wild-type controls were isolated, cannulated with micropipettes, an ...[more]

PMID: 19407017

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Project description:We tested the hypothesis that the M3 muscarinic acetylcholine receptor subtype mediates cholinergic responses in murine ophthalmic arteries after endothelial removal.Muscarinic receptor gene expression was determined in ophthalmic arteries with intact and with removed endothelium using real-time PCR. To examine the role of the M3 receptor in mediating vascular responses, ophthalmic arteries from M3 receptor-deficient mice (M3R(-/-)) and respective wild-type controls were studied in vitro. Functional studies were performed in nonpreconstricted arteries with either intact or removed endothelium using video microscopy.In endothelium-intact ophthalmic arteries, mRNA for all five muscarinic receptor subtypes was detected, but M3 receptor mRNA was most abundant. In endothelium-removed ophthalmic arteries, M1, M2, and M3 receptors displayed similar mRNA expression levels, which were higher than those for M4 and M5 receptors. In functional studies, acetylcholine evoked vasoconstriction in endothelium-removed arteries from wild-type mice that was virtually abolished after incubation with the muscarinic receptor blocker atropine, indicative of the involvement of muscarinic receptors. In concentration-response experiments, acetylcholine and carbachol concentration-dependently constricted endothelium-removed ophthalmic arteries from wild-type mice, but produced only negligible responses in arteries from M3R(-/-) mice. In contrast, acetylcholine concentration-dependently dilated ophthalmic arteries with intact endothelium from wild-type mice, but not from M3R(-/-) mice. Responses to the nitric oxide donor nitroprusside and to KCl did not differ between ophthalmic arteries from wild-type and M3R(-/-) mice, neither in endothelium-intact nor in endothelium-removed arteries.These findings provide evidence that in murine ophthalmic arteries the muscarinic M3 receptor subtype mediates cholinergic endothelium-dependent vasodilation and endothelium-independent vasoconstriction.

Dataset Information

Cholinergic responses of ophthalmic arteries in M3 and M5 muscarinic acetylcholine receptor knockout mice.

Publications

Cholinergic responses of ophthalmic arteries in M3 and M5 muscarinic acetylcholine receptor knockout mice.

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