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M C Scrutton

Publications and source records attributed to M C Scrutton.

113 records · Page 7Linked to original sources
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A plea for a comparative approach to evaluation of the physiological significance of regulatory mechanism observed in in vitro studies.

Regulatory mechanisms proposed on the vasis of in vitro studies using purified enzymes should be evaluated for their physiological significance in different species and under various conditions. The procedures presently employed for such evaluation are examined, and it is suggested that difficulties of application or interpretation arise, especially in studies on highly differentiated organisms. The use of comparative enzymology as an alternative approach to this problem is proposed, using in the main data obtained in studies on pyruvate carboxylase to illustrate the potential of this method. Some problems which arise in the use of comparative studies in this context are considered.

Animals↗
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Cyclic nucleotides control a system which regulates Ca2+ sensitivity of platelet secretion.

Cellular responses to extracellular signals are mediated by changes in the intracellular concentrations of one or more second messengers. In platelets, inhibitory agonists increase intracellular cyclic-3',5'-AMP [( cyclic AMP]i (refs 2, 3] whereas excitatory agonists increase [Ca2+]i and/or [1,2-diacylglycerol]i (refs 4-9), and in some cases decrease [cyclic AMP]i (refs 10, 11). Both activation and inhibition of platelet responses have been attributed to an increase in [cyclic-3',5'-GMP]i (refs 8, 12). The activity of protein kinase C, which is associated with the platelet secretory response, is increased by both 1,2-diacylglycerol and Ca2+ (refs 4, 7, 8). The role of cyclic AMP may involve either inhibition of Ca2+ mobilization to the cytosol or stimulation of intracellular Ca2+ uptake, and in addition inhibition of 1,2-diacylglycerol formation. The relationship between cyclic-3',5'-GMP (cyclic GMP) and other second messengers in platelet activation has not been defined. Using platelets made permeable by exposure to an intense electric field, we demonstrate here modulation of the Ca2+ sensitivity of platelet secretion by thrombin, and by 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-oleyl-2- acetylglycerol ( OAG ), both potent activators of protein kinase C. The effect of thrombin is selectively modified by cyclic GMP and cyclic AMP. The response to OAG and TPA is also modulated by cyclic AMP but to a much lesser extent.

1-Methyl-3-isobutylxanthine↗