Biochemistry of Signal Transduction in Myocardium by Han A. A. van Heugten, Yvonne E. G. Eskildsen-Helmond,

By Han A. A. van Heugten, Yvonne E. G. Eskildsen-Helmond, Henriette W. de Jonge (auth.), Jos M. J. Lamers, Pieter D. Verdouw (eds.)

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PLC-~2 or -~3 were equally effective (G. M. ). Two other prominent effects ofPLC-~l were observed. In the absence ofPLC-~l' atropine did not inhibit GTPase activity until -1 min after addition, whereas termination was immediate in the presence ofPLC-~l [32]. Second, the onset ofCCh-stimulated GTP hydrolysis was not affected, but lO-foldmoreCCh(lS ~ was needed to elicit half maximum stimulation of steady-state GTP hydrolysis, in the presence ofPLC-~l [32]. This indicated that the rate-limiting step in the basal cycle of Gq is GTP hydrolysis and that it is switched to a receptor-dependent step by PLC-~.

Functions of cGKs Relaxation of smooth muscle cells Smooth muscle contraction has been shown to depend on phosphorylation of the regulatory light chain of myosin, by a specific myosin light chain kinase (MLCK). Since MLCK is activated by Ca/calmodulin, smooth muscle contraction is initiated primarily by a rise in intracellular free Ca level, as provoked by many contractile agents [54]. The cGMP-induced reduction of intracellular Ca, observed in many studies is therefore considered an important mechanism of cGMP-mediated relaxation.

Agonists, such as endothelin-l, atrial natriuretic factor and angiotensin II that are shown to activate phospholipase D, also potently stimulate phospholipase C-~ in myocardium. PMA stimulation of protein kinase C inactivates phospholipase C and strongly activates phospholipase D and this is probably a major mechanism by which agonists that promote phosphatidyl-4,5-bisphosphate hydrolysis secondary activate phosphatidylcholine-hydrolysis. On the other hand, one group has postulated that formation of phosphatidic acid secondary activates phosphatidyl-4,5-bisphosphate hydrolysis in cardiomyocytes.

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