27 part 2. Laith Abu Shekha. Mamoon Al-qatameen

Transcription

1 27 part 2 Laith Abu Shekha Mamoon Al-qatameen Ebaa Alzayadneh

2 In this sheet we will continue talking about second messengers for hormone that can t cross PM. D. Ca +2 as a second messenger: Another second messenger system operates in response to the entry of calcium into the cells, calcium entry may be initiated by: 1) changes in membrane potential 2) A hormone interacting with membrane receptor that open calcium channel Upon entering a cell calcium ions bind with the protein calmodulin, the calmodulin changes its shape and initiates multiple effects inside the cell, including activation or inhibition of protein kinases Activation of calmodulin dependent protein kinases cause via phosphorylation activation or inhibition of proteins involved in the cells response to the hormone 1 P a g e

3 This shows the calcium calmodulin, calcium is important in cytosol it could bind with calmodulin and the calmodulin will activates different kinases, and make changes in the metabolism of the cell. The picture below shows the activation of calmodulin: Nitric oxide signaling: Nitric oxide signaling is very important because the nitric oxide is important in signaling, nitric oxide is an anti-dilator and it s a vasodilator signal platelet derive relaxing factor, and it called anti-placement adhesion. Nitric oxide is a signaling molecule which transferred signals, it can produced easily in the cell membrane. In this example which is required, there is blood vessel wall, endothelial cells layer and smooth muscle cells layer, usually its one mole of arteriole not capillary, it may be an arteriole or an artery which has endothelial or smooth muscle cells layer, in endothelial cell layer the signal produce the nitric oxide the signal is usually an acetylcholine that will bind to G-Protein couple receptors (Gq) so it will activates phospholipase C by reducing (releasing) calcium, calcium is released by calmodulin, which activates an enzyme that can produce the nitric oxide and it called nitric oxide synthase. Nitric oxide make vasodilation which 2 P a g e

4 leads to increase the flow of the blood and this one of the important function of nitric oxide. Note that calmodulin complex activates the nitric oxide in endothelial cell producing NO from an amino acid called arginine. Nitric oxide will defuse into the smooth muscle cells to do the vasodilating action (relaxation of the smooth muscle cells), that will act by inducing signaling, so it was produced by signaling and now it will induce signaling. Note: signaling is a production of camp, the soluble form of cyclase will be activated and it will be found in the cytosol, so it will produce cgmp as a second messenger, now هيك حكت الدكتورة بالمحاضرة ( G. cgmp will activate protein kinase In my opinion: 1) NO can easily diffuse short distances and affect more than one cells 2) Causes relaxation in vascular smooth muscles, leading to blood vessel dilation 3) Activates an intercellular enzyme, soluble guanylyl cyclase to catalyze the second messenger (c GMP), (c GMP) activates protein kinase G 4) In smooth muscle cells, this leads to decrease in Ca+2 in the cytosol to cause relaxation of the smooth muscle and blood vessel dilation 5) Found in neurons and immune system, either acting within the cell in which it is produced or by penetrating cell membranes to affect adjacent cells (local mediators) 6) It soluble in both aqueous and lipid media, it readily diffuses through the cytoplasm and plasma membrane 7) NO has some effects such as antimicrobial cytotoxic and inflammatory 3 P a g e

5 *the (cgmp) is degraded by phosphodiesterase *** KG is cgmp dependent, which induce relaxation of the smooth muscle cells that leads to reduce the cell surface of the blood vessel. There is another example on the cgmp which is atrial natriuretic peptide (ANP), it is an also vasodilator and the second messenger for it is cgmp, so the nitric oxide and the atrial natriuretic peptide (atrial natriuretic factor (ANF)) Aims to decrease pressure by vasodilation and this is its second messenger Now we will move to the last type of second messenger: E. PIP3: PIP3 is basically PIP2, so PIP3 is a PIP2 phosphorylated by PI 3- Kinase resulting PIP3, which is a second messenger, PIP3 derived from the plasma membrane. *** This picture below shows how different pathways can be activated by different ligands and different receptors, so the same enzyme can be activated by more than one signaling pathway (signaling molecule). 4 P a g e

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