Diacylglycerol muscle stimulation

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

The diacylglycerols released by phospholipase C diffuse laterally through the bilayer and, together with the incoming Ca2+, activate protein kinases C. These kinases also require phosphatidylserine for their activity and phosphorylate serine and threonine side chains in a variety of proteins.329 330b They are stimulated by the released unsaturated diacylglycerols. In addition protein kinases C can be activated by phorbol esters, which are the best known tumor promoters (Box 11-D). The diacylglycerol requirement favors a function for these protein kinases in membranes. They also appear to cooperate with calmodulin to activate the Ca2+-dependent contraction of smooth muscle.330... 

Griendling, K. K., Rittenhouse, S. E., Brock, T. A., et al. 1986. Sustained diacylglycerol formation from inositol phospholipids in angiotensin II-stimulated vascular smooth muscle cells. J Biol Chem 261 5901-5906. 

Activation of phospholipase C leads to cleavage of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate into inositol trisphosphate (IP3) and diacylglycerol (DAG). 1P3 promotes release of Ca2+ from storage organelles, whereby contraction of smooth muscle cells, breakdown of glycogen, or exocytosis may be initiated. DAG stimulates protein kinase C, which phosphorylates certain serine- or threonine-containing enzymes. 

H.Y. Yu, T. Inoguchi, M. Kakimoto, N. Nakashima, M. Imamura, T. Hashimoto, F. Umeda, and H. Nawata, Saturated non-esterified fatty acids stimulate de novo diacylglycerol synthesis and protein kinase C activity in cultured aortic smooth muscle cells, Diabetologia, 2001, 44, 614—620. 

The answer is c. (Murray, pp 238-249. Scriver, pp 2367-2424. Sack, pp 159-175. Wilson, pp 287-317.) A variety of agonists activate the plasma membrane-bound enzyme phospholipase C, which hydrolyzes the phosphodiester bond of phosphatidyl inositol 4,5-bisphosphate and consequently releases diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). Phospholipase C is also known as phosphoinositidase and as polyphosphoinositide phosphodiesterase. Both DAG and IP3 are second messengers. DAG activates protein kinase C, which is important in controlling cell division and cell proliferation. IP3 opens calcium channels and allows the rapid release of the calcium stores in endoplasmic reticulum (in smooth muscle, sarcoplasmic reticulum). The elevated levels of calcium ion stimulate smooth-muscle contraction, exocytosis, and glycogen breakdown. 

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