Agonists differentiate muscarinic receptors that inhibit cyclic AMP formation from those that stimulate phosphoinositide metabolism.

作者: J H Brown , S L Brown

DOI: 10.1016/S0021-9258(17)43162-0

关键词: CyclaseMuscarinic acetylcholine receptorChemistryOxotremorineReceptorCarbacholEndocrinologyMuscarinic acetylcholine receptor M5Adenylate kinaseInternal medicineBiophysicsAgonistCell biologyBiochemistryMolecular biology

摘要: Muscarinic receptor stimulation elicits two distinct biochemical responses in embryonic chick heart cells: inhibition of catecholamine-stimulated cyclic AMP formation and phosphoinositide (PhI) hydrolysis. We observe major differences the effects agonists on these responses. First, carbachol oxotremorine both inhibit formation, but only stimulates PhI Second, dose-response relationships for differ; half-maximal concentrations needed to cAMP accumulation stimulate hydrolysis are 2 X 10(-7) 10(-5) M, respectively. carried out radioligand binding studies intact cells determine whether data could be explained terms different agonist states muscarinic receptor. In cells, competes [3H]quinuclidinyl benzilate-binding sites with high low affinity, while shows affinity binding. suggest that state common is associated adenylate cyclase, very site seen response. also consider possibility caused by a single efficiently coupled cyclase inefficiently Whichever mechanism correct, our findings demonstrate receptors response can differentiated virtue their sensitivity efficiency which some induce change elicit receptor-mediated

参考文章(27)
L R Jones, J W Fleming, A M Watanabe, H R Besch, M M McConnaughey, R A Strawbridge, Muscarinic cholinergic receptor modulation of beta-adrenergic receptor affinity for catecholamines. Journal of Biological Chemistry. ,vol. 253, pp. 4833- 4836 ,(1978) , 10.1016/S0021-9258(17)34620-3
P A Insel, L C Mahan, H J Motulsky, L M Stoolman, A M Koachman, Time-dependent decreases in binding affinity of agonists for beta-adrenergic receptors of intact S49 lymphoma cells. A mechanism of desensitization. Journal of Biological Chemistry. ,vol. 258, pp. 13597- 13605 ,(1983) , 10.1016/S0021-9258(17)43957-3
J.Z. Fields, W.R. Roeske, E. Morkin, H.I. Yamamura, Cardiac muscarinic cholinergic receptors. Biochemical identification and characterization. Journal of Biological Chemistry. ,vol. 253, pp. 3251- 3258 ,(1978) , 10.1016/S0021-9258(17)40829-5
S K Fisher, P D Klinger, B W Agranoff, Muscarinic agonist binding and phospholipid turnover in brain. Journal of Biological Chemistry. ,vol. 258, pp. 7358- 7363 ,(1983) , 10.1016/S0021-9258(18)32186-0
A. S. V. Burgen, N. J. M. Birdsall, E. C. Hulme, The binding of agonists to brain muscarinic receptors. Molecular Pharmacology. ,vol. 14, pp. 723- 736 ,(1978)
M J Berridge, C P Downes, M R Hanley, Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands Biochemical Journal. ,vol. 206, pp. 587- 595 ,(1982) , 10.1042/BJ2060587