Batty I H, Nahorski S R
Department of Pharmacology and Therapeutics, University of Leicester, U.K.
Biochem J. 1989 May 15;260(1):237-41. doi: 10.1042/bj2600237.
The rapid kinetics of [3H]inositol phosphate accumulation and turnover were examined in rat cerebral-cortex slices after muscarinic-receptor stimulation. Markedly increased [3H]inositol polyphosphate concentrations were observed to precede significant stimulated accumulation of [3H]inositol monophosphate. New steady-state accumulations of several 3H-labelled products were achieved after 5-10 min of continued agonist stimulation, but were rapidly and effectively reversed by subsequent receptor blockade. The results show that muscarinic-receptor activation involves phosphoinositidase C-catalysed hydrolysis initially of polyphosphoinositides rather than of phosphatidylinositol. Furthermore, prolonged carbachol stimulation is shown not to cause receptor desensitization, but to allow persistent hydrolysis of [3H]phosphatidylinositol bisphosphate and permit sustained metabolic flux through the inositol tris-/tetrakis-phosphate pathway.
在毒蕈碱受体刺激后,对大鼠大脑皮层切片中[3H]肌醇磷酸积累和周转的快速动力学进行了研究。观察到[3H]肌醇多磷酸浓度显著增加先于[3H]肌醇单磷酸的显著刺激积累。在持续激动剂刺激5-10分钟后,几种3H标记产物达到新的稳态积累,但随后的受体阻断可迅速有效地逆转这种积累。结果表明,毒蕈碱受体激活最初涉及磷酸肌醇酶C催化的多磷酸肌醇而非磷脂酰肌醇的水解。此外,长时间的卡巴胆碱刺激未导致受体脱敏,而是允许[3H]磷脂酰肌醇二磷酸的持续水解,并允许通过肌醇三磷酸/四磷酸途径的持续代谢通量。