完整灌注大鼠心脏中受体刺激的磷脂酰肌醇水解的研究。

Study of receptor-stimulated phosphatidylinositol hydrolysis in intact, perfused rat hearts.

Woodcock E A, McLeod J K, Smith A I, Clark M G

Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Victoria, Australia.

Clin Exp Pharmacol Physiol. 1987 Mar;14(3):209-13. doi: 10.1111/j.1440-1681.1987.tb00377.x.

Abstract

Phosphatidylinositol turnover has been measured in intact, perfused rat hearts by measuring generation of inositol phosphates following [3H]-inositol labelling. Stimulation of accumulations of inositol monophosphate, inositol bisphosphate and inositol trisphosphate were observed during perfusion with either noradrenaline (3 X 10(-5) mol/l) or carbachol (10(-3) mol/l). 2. Stimulation by noradrenaline was antagonized by prazosin (10(-7) mol/l) but not by propranolol (10(-7) mol/l), indicating mediation via alpha 1-adrenoceptors. Stimulation by carbachol was antagonized by atropine (10(-7) mol/l). 3. Transmural electrical stimulation of the hearts failed to increase inositol phosphate accumulation through alpha 1-adrenoceptors. A small stimulation mediated by muscarinic receptors was observed. Therefore alpha 1-adrenoceptors which stimulate phosphatidylinositol turnover probably do not have a synaptic localization in heart. 4. The development of methods for the study of phosphatidylinositol turnover in intact hearts will facilitate an investigation of relationships between this signal transduction pathway and cardiac function.

摘要

通过测量[3H]-肌醇标记后肌醇磷酸的生成，已在完整的灌注大鼠心脏中测定了磷脂酰肌醇周转率。在用去甲肾上腺素（3×10⁻⁵mol/L）或卡巴胆碱（10⁻³mol/L）灌注期间，观察到肌醇一磷酸、肌醇二磷酸和肌醇三磷酸的积累受到刺激。2. 去甲肾上腺素的刺激作用被哌唑嗪（10⁻⁷mol/L）拮抗，但未被普萘洛尔（10⁻⁷mol/L）拮抗，表明其通过α1-肾上腺素能受体介导。卡巴胆碱的刺激作用被阿托品（10⁻⁷mol/L）拮抗。3. 心脏的跨壁电刺激未能通过α1-肾上腺素能受体增加肌醇磷酸的积累。观察到由毒蕈碱受体介导的小刺激。因此，刺激磷脂酰肌醇周转率的α1-肾上腺素能受体可能在心脏中没有突触定位。4. 完整心脏中磷脂酰肌醇周转率研究方法的发展将有助于研究这种信号转导途径与心脏功能之间的关系。