Karaalp A, Akici A, Akbulut H, Ulusoy N B, Oktay S
Department of Pharmacology and Clinical Pharmacology, Marmara University School of Medicine, Istanbul, Haydarpaşa, 81326, Turkey.
Pharmacol Res. 1999 May;39(5):389-95. doi: 10.1006/phrs.1999.0453.
The contractile responses of guinea-pig gallbladder smooth muscle cells have been suggested to be mediated by M3 and M4 muscarinic receptors by different research groups. Therefore, in the present study, several pharmacological properties of cholinergic functions in guinea-pig gallbladder, guinea-pig ileum (mediated via M3 receptors), and guinea-pig and rat atria (mediated via M2 receptors) were compared.
The isometric contractions of isolated guinea-pig ileum, guinea-pig gallbladder, guinea-pig and rat atrial strips in in vitro organ bath were recorded on a polygraph and the effects of carbachol, oxotremorine, McN-A-343, and clozapine have been investigated.
Three muscarinic receptor agonists, carbachol, oxotremorine and McN-A-343 showed different order of potencies in their negative inotropic effects and contractile actions in guinea-pig gallbladder suggesting that functional muscarinic receptors in the gallbladder are distinct from those in the atria, and similar to M4-subtypes. Clozapine which was shown to have antagonistic affinity for muscarinic M1, M2, M3 and M5, but partial agonistic affinity for muscarinic M4 receptors, contracted gallbladder concentration-dependently. On the other hand, clozapine antagonised carbachol-induced ileal and gallbladder contractions and negative inotropic effects indicating that it acts like a partial agonist in the gallbladder.
It was concluded that the contractile muscarinic receptors of guinea-pig gallbladder are distinct from those of atria (M2) and ileum (M3), but seem to be of M4 subtype.
不同研究小组认为豚鼠胆囊平滑肌细胞的收缩反应由M3和M4毒蕈碱受体介导。因此，在本研究中，比较了豚鼠胆囊、豚鼠回肠（由M3受体介导）以及豚鼠和大鼠心房（由M2受体介导）中胆碱能功能的几种药理学特性。
在体外器官浴中记录分离的豚鼠回肠、豚鼠胆囊、豚鼠和大鼠心房条带的等长收缩，用多导生理记录仪进行记录，并研究了卡巴胆碱、氧化震颤素、McN-A-343和氯氮平的作用。
三种毒蕈碱受体激动剂，即卡巴胆碱、氧化震颤素和McN-A-343，在豚鼠胆囊中的负性变力作用和收缩作用表现出不同的效价顺序，这表明胆囊中的功能性毒蕈碱受体与心房中的不同，与M4亚型相似。氯氮平对毒蕈碱M1、M2、M3和M5具有拮抗亲和力，但对毒蕈碱M4受体具有部分激动亲和力，它能使胆囊浓度依赖性收缩。另一方面，氯氮平拮抗卡巴胆碱诱导的回肠和胆囊收缩以及负性变力作用，表明它在胆囊中表现为部分激动剂。
得出的结论是，豚鼠胆囊的收缩性毒蕈碱受体与心房（M2）和回肠（M3）的不同，但似乎属于M4亚型。
