The innermost layer of the blood vessels in the endothelium is also called the tunica intima. the middle layer is tunica media which has smooth muscles. The last layer is the tunica adventitia, which is composed of collagen. The activated nerve terminal secretes the neurotransmitter, acetylcholine. The endothelial cells have GPCRs (G-protein coupled receptors). The GPCRs receives the acetylcholine molecules. It brings conformational changes in the receptor and the G-protein is activated. It in turn generates a cascade of signals. The cascade of signals has PLC (phospholipase C) which converts the phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol phosphate (IP3) and diacylglycerol (DAG). The IP3 is soluble in the cytoplasm and it acts as a secondary messenger. The IP3wasthen transported to the receptors in the smooth muscle. IP3 stimulates the opening of calcium ion channels. The calcium ions are then released from the sarcoplasmic reticulum. DAG is insoluble and it remains in the cell membrane. The calcium released from the sarcoplasmic reticulum activates the calmodulin protein. The calmodulin protein is called calcium modulated protein. It has a property to activate the NOS. NOS synthesizes nitric oxide from arginine in the endothelial cells. Nitric oxide then diffuses into the smooth muscles. Nitic oxide combines with the heme group of guanylcyclase in smooth muscle cells and activates the guanylcyclase enzyme. This enzyme converts the GTP (guanosine triphosphate) into cyclic guanosine monophosphate (cGMP). This cGMP stimulates cGMP dependent protein kinase. This phosphorylates myosin light chain kinase (MLCK). MLCK dephosphorylates the myosin light chain and inhibits the contraction of smooth muscle and keeps them relaxed.
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