Shi X Z, Sarna S K
Departments of Surgery and Physiology, Medical College of Wisconsin Milwaukee, Wisconsin 53295, USA.
Am J Physiol. 1999 Aug;277(2):G341-50. doi: 10.1152/ajpgi.1999.277.2.G341.
The aim of this study was to identify the subtypes of muscarinic receptors that mediate in vivo and in vitro canine ileal longitudinal muscle contractions and whether their role is modulated by inflammation. Previous studies have reported that circular muscle contractions are suppressed in ileal inflammation induced by mucosal exposure to ethanol and acetic acid. We found that inflammation had no significant effect on in vivo and in vitro spontaneous or muscarinic receptor-mediated contractions of the longitudinal muscle. The longitudinal muscle contractions were mediated primarily by the M(3) receptor subtype. However, the IC(50) of the M(2) receptor antagonist methoctramine was only 10 times greater than that of the M(3) receptor antagonist 4-DAMP in the longitudinal muscle, whereas it was 224 times greater in the circular muscle. M(2) receptor-coupled decrease of intracellular cAMP occurred in the longitudinal but not in the circular muscle from the normal ileum. Inflammation did not alter this coupling in the longitudinal muscle but established it in the circular muscle. In conclusion, M(2) receptors may play a greater role in the mediation of longitudinal muscle contractions than circular muscle contractions. Inflammation does not alter the contractility or the relative role of muscarinic receptor subtypes in longitudinal muscle cells. However, it modulates the M(2) receptor coupling to adenylate cyclase in the circular muscle.
本研究的目的是确定介导犬回肠纵肌体内和体外收缩的毒蕈碱受体亚型，以及它们的作用是否受炎症调节。先前的研究报道，黏膜暴露于乙醇和乙酸所诱导的回肠炎症会抑制环肌收缩。我们发现，炎症对纵肌的体内和体外自发收缩或毒蕈碱受体介导的收缩均无显著影响。纵肌收缩主要由M(3)受体亚型介导。然而，在纵肌中，M(2)受体拮抗剂美索曲明的IC(50)仅比M(3)受体拮抗剂4-DAMP的IC(50)大10倍，而在环肌中则大224倍。正常回肠纵肌中发生了M(2)受体偶联的细胞内cAMP减少，而环肌中未发生。炎症并未改变纵肌中的这种偶联，但在环肌中建立了这种偶联。总之，M(2)受体在介导纵肌收缩方面可能比环肌收缩发挥更大的作用。炎症不会改变纵肌细胞中毒蕈碱受体亚型的收缩性或相对作用。然而，它会调节环肌中M(2)受体与腺苷酸环化酶的偶联。
