Both M(1) and M(3) receptors regulate exocrine secretion by mucous acini
Both M(1) and M(3) receptors regulate exocrine secretion by mucous acini
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DOI：
10.1152/ajpcell.1996.271.6.c1963
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发表时间：
1996-12-01
影响因子：
5.5
通讯作者：
Latchney, LR
中科院分区：
文献类型：
--
作者：
Culp, DJ;Luo, W;Latchney, LR
我们研究了M（1）和M（3）受体在调节大鼠舌下腺腺泡外分泌中的作用。在分泌实验中，我们从Schild回归分析中推导出拮抗剂哌仑西平（61.0 nM）和4-二苯基乙酰氧基-N-甲基哌啶（4-DAMP; 1.06 nM）的亲和力值（K-B）。4-DAMP的K-B与放射性配体竞争实验测定的亲和力值[竞争研究的平衡解离常数（Ki）; 1.81 nM]相似。相比之下，哌仑西平的K-B在其高亲和力（17.6 nM）和低亲和力（404 nM）K-i值之间。在单独的分泌实验中，我们发现M（1）受体拮抗剂，M（1）-毒素，诱导毒蕈碱激动剂的浓度-反应曲线的一次移动，并抑制40%的最大分泌。M（1）-毒素的抑制作用似乎对M（1）受体阻断具有特异性，因为该毒素消除了腺泡高亲和力哌仑西平结合位点，并且不抑制非毒蕈碱药物诱导的分泌。其他药理学研究表明，毒蕈碱受体不通过孤立的腺泡内的假定神经元件发挥作用。我们的综合结果与M（1）和M（9）受体直接调节粘液腺泡外分泌一致，并表明M（3）受体单独不足以诱导最大的毒蕈碱反应。
We investigated the role of M(1) and M(3) receptors in regulating exocrine secretion from acini isolated from rat sublingual glands. In secretion experiments, we derived affinity values (K-B) from Schild regression analysis for the antagonists pirenzepine (61.0 nM) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 1.06 nM). The K-B for 4-DAMP is similar to its affinity value [equilibrium dissociation constant from competition studies (K-i); 1.81 nM] determined from radioligand competition experiments. In contrast, the K-B for pirenzepine is between its high-affinity (17.6 nM) and low-affinity (404 nM) K-i values. In separate secretion experiments, we found that the M(1) receptor antagonist, M(1)-toxin, induces a rightward shift in the concentration-response curve to muscarinic agonist and inhibits maximal secretion by 40%. The inhibitory effect of M(1)-toxin appears specific for M(1) receptor blockade, since the toxin abolishes acinar high-affinity pirenzepine-binding sites and does not inhibit secretion induced by nonmuscarinic agents. Additional pharmacological studies indicate muscarinic receptors do not function through putative neural elements within isolated acini. Our combined results are consistent with both M(1) and M(9) receptors directly regulating mucous acinar exocrine secretion and indicate M(3) receptors alone are insufficient to induce a maximal muscarinic response.