Functional activation of G-proteins coupled with muscarinic acetylcholine receptors in rat brain membranes.
Yuji Odagaki, Masakazu Kinoshita, Ryoichi Toyoshima
文献索引:J. Pharmacol. Sci. 125(2) , 157-68, (2014)
全文:HTML全文
摘要
The functional activation of Gi/o proteins coupled to muscarinic acetylcholine receptors (mAChRs) was investigated with the conventional guanosine-5'-O-(3-[(35)S]thio) triphosphate ([(35)S]GTPγS) binding assay in rat brain membranes. The most efficacious stimulation elicited by acetylcholine or carbachol (CCh) was obtained in striatal membranes. The pharmacological properties of mAChR-mediated [(35)S]GTPγS binding determined with a series of muscarinic agonists and antagonists were almost identical among the three brain regions investigated, i.e., cerebral cortex, hippocampus, and striatum, except for the apparent partial agonist effects of (αR)-α-cyclopentyl-α-hydroxy-N-[1-(4-methyl-3-pentenyl)-4-piperidinyl]benzeneacetamide fumarate (J 104129) observed only in the hippocampus, but not in the other two regions. Among the muscarinic toxins investigated, only MT3 attenuated CCh-stimulated [(35)S] GTPγS binding. The highly selective allosteric potentiator at the M4 mAChR subtype, 3-amino-N-[(4-chlorophenyl)methyl]-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide (VU 10010), shifted the concentration-response curve for CCh leftwards as well as upwards. On the other hand, neither thiochrome nor brucine N-oxide was effective. The increases induced by CCh and 5-HT were essentially additive, though not completely, indicating that the mAChRs and 5-HT1A receptors were coupled independently to distinct pools of Gi/o proteins. Collectively, all of the data suggest that functional activation of Gi/o proteins coupled to mAChRs, especially the M4 subtype, is detectable by means of CCh-stimulated [(35)S]GTPγS binding assay in rat discrete brain regions.
相关化合物
相关文献:
2015-04-23
[Neurosci. Lett. 593 , 129-33, (2015)]
2015-02-25
[J. Neurosci. 35(8) , 3676-88, (2015)]
2009-10-01
[Naunyn Schmiedebergs Arch. Pharmacol. 380(4) , 327-35, (2009)]
2010-01-01
[Biol. Pharm. Bull. 33(4) , 653-8, (2010)]
2012-06-01
[Acta Biochim. Biophys. Sin. (Shanghai) 44(6) , 544-9, (2012)]