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Acta Physiologica 2009; Volume 195, Supplement 669
The 88th Annual Meeting of The German Physiological Society
3/22/2009-3/25/2009
Giessen, Germany
IMPACT OF M3 AND M5 ACETYLCHOLINE RECEPTORS ON CHOLINERGIC DILATATION OF MESENTERIC ARTERIES IN GENETICALLY MODIFIED MICE
Abstract number: YP34
Mayer1 V., Steege2 A., Patzak2 A., Grus1 F. H., Joachim1 S. C., Choritz1 L., Wess3 J., Pfeiffer1 N., Gericke1 A.
1Department of Ophthalmology, Johannes-Gutenberg University, Mainz
2Institute of Vegetative Physiology, University Hospital Charit, Berlin
3Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States of America
Objective:
Acetylcholine regulates perfusion of numerous organs via changes in local blood flow involving muscarinic receptor-induced release of nitric oxide. So far, five muscarinic receptor subtypes (M1-M5) have been identified. Previous studies suggest that cholinergic responses of cerebral arteries are mediated by M5, and those of extra-cerebral blood vessels predominantly by M3 receptors. However, as yet, the functional relevance of muscarinic receptor subtypes has not been defined in the major extra-cerebral vascular resistance beds. Thus, the purpose of this study was to determine the muscarinic receptors mediating cholinergic responses in small mesenteric arteries using gene-targeted mice.
Methods and Results:
Receptor gene expression was quantified in isolated murine mesenteric arteries using RT-PCR. Levels of M3 and M5 mRNA were the highest, although mRNA of all 5 muscarinic receptor subtypes was detected. To test the functional relevance of M3 and M5 receptors, mesenteric arteries from mice deficient in either receptor subtype (M3R-/-, M5R-/-, respectively) and wild-type controls were isolated, cannulated with micropipettes and pressurized. Luminal diameter was measured using video microscopy. After preconstriction with phenylephrine, acetylcholine produced dose-dependent dilation of mesenteric arteries that was similar in M5R-/- and wild-type mice (394% and 423% at 10 mM; M5R-/- vs. wild-type mice; P>0.05). In contrast, cholinergic dilation of mesenteric arteries was markedly reduced in M3R-/- mice (244% at 10 mM; M3R-/- vs. M5R-/- and wild-type mice; P<0.05). Deletion of either M3 or M5 receptor did not affect responses to non-muscarinic vasodilators, such as bradykinin or nitroprusside.
Conclusion:
These findings provide the first direct evidence that M3 receptors are profoundly involved in cholinergic regulation of diameter in murine mesenteric arteries. However, the residual vascular response in M3R-/- mice also suggests the involvement of another subtype in the cholinergic dilatory response of mesenteric vessels.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 669 :YP34