Hoover D B, Baisden R H, Xi-Moy S X
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614.
Circ Res. 1994 Nov;75(5):813-20. doi: 10.1161/01.res.75.5.813.
Although the heart is considered a relatively pure source of m2 muscarinic receptors, the possible expression of other muscarinic receptor genes at discrete sites within the myocardium or by intrinsic cardiac ganglia had not been evaluated. Accordingly, the present study used in situ hybridization histochemistry with 35S-labeled oligonucleotide probes to address this issue. Initial experiments demonstrated that the localization of m2 mRNA was similar to that reported for muscarinic receptors labeled with the nonselective muscarinic antagonist quinuclidinyl benzilate; however, there were two important exceptions. The conducting system contained less message than expected, whereas the intrinsic cardiac ganglia contained more. The mismatch between muscarinic receptor and m2 mRNA densities in the conducting system could not be explained by the local expression of other muscarinic receptor genes, since m1, m3, and m4 mRNAs were not detected at this or any other site within the myocardium. However, the presence of a high density of prejunctional muscarinic receptors in the conducting system would be consistent with such a mismatch. Surprisingly, the intrinsic cardiac ganglia contained more than four times as much m2 mRNA as found in the atria. This level of message may be necessary for the production of prejunctional receptors on cholinergic nerve fibers within the heart and receptors localized to the ganglion cell bodies. The ganglia also contained smaller amounts of m1 and m4 mRNAs. These observations suggest that prejunctional muscarinic receptors could have a prominent role in regulating cholinergic neurotransmission in the conducting system and that multiple muscarinic receptors are present in the intrinsic cardiac ganglia.
尽管心脏被认为是M2毒蕈碱受体相对纯净的来源，但心肌内离散部位或心脏固有神经节中其他毒蕈碱受体基因的可能表达尚未得到评估。因此，本研究使用35S标记的寡核苷酸探针进行原位杂交组织化学来解决这个问题。初步实验表明，M2 mRNA的定位与用非选择性毒蕈碱拮抗剂喹核醇基苯甲酸酯标记的毒蕈碱受体的报道相似；然而，有两个重要的例外。传导系统中的信息比预期的少，而心脏固有神经节中的信息更多。传导系统中毒蕈碱受体和M2 mRNA密度之间的不匹配不能用其他毒蕈碱受体基因的局部表达来解释，因为在心肌的这个或任何其他部位都未检测到M1、M3和M4 mRNA。然而，传导系统中存在高密度的节前毒蕈碱受体与这种不匹配是一致的。令人惊讶的是，心脏固有神经节中的M2 mRNA含量是心房中的四倍多。这种信息水平对于心脏内胆碱能神经纤维上节前受体以及位于神经节细胞体上的受体的产生可能是必要的。神经节中还含有少量的M1和M4 mRNA。这些观察结果表明，节前毒蕈碱受体可能在调节传导系统中的胆碱能神经传递中起重要作用，并且心脏固有神经节中存在多种毒蕈碱受体。
