Diacylglycerol may act as a second messenger mediating the effects of acetylcholine on high-threshold voltage-activated Ca2+ channels in smooth muscle cells via protein kinase C activation.
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May link acetylcholine to PKC-mediated Ca2+ currents in animal smooth muscle; leaves open relevance to human vascular disease or therapy.
Electrophysiological recordings from freshly dissociated smooth muscle cells from the stomach of the toad Bufo marinus revealed two types of Ca 2+ currents. One has a low threshold of activation and inactivates rapidly; the other has a high threshold of activation and inactivates more slowly. Acetylcholine (ACh) increased the high‐threshold current but not the low‐threshold current. The synthetic diacylglycerol analog sn ‐1,2‐dioctanoylglycerol, an activator of protein kinase C (PKC), mimicked these effects of ACh on Ca 2+ currents. However, another diacylglycerol analog, 1,2‐dioctanoyl‐3‐thioglycerol, which has a closely related structure but does not activate PKC, failed to increase the Ca 2+ current. The same was true of l,2‐dioctanoyl‐3‐chloropropanediol, an analog that even at high concentrations only minimally activates PKC. These results suggest that diacylglycerol may be the second messenger mediating the effects of ACh on one type of voltage‐activated Ca 2+ channel, possibly by activating PKC.— V ivaudou , M. B.; C lapp , L. H.; W alsh , J. V., J r .; S inger , J. J. Regulation of one type of Ca 2+ current in smooth muscle cells by diacylglycerol and acetylcholine. FASEB J. 2: 2497‐2504; 1988.
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Vivaudou et al. (1988) studied this question.
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