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What are Second Messengers?01:12

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Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
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Amplifying Signals via Second Messengers01:15

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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
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GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
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3',5'-cIMP as Potential Second Messenger in the Vascular Wall.

Susan W S Leung1, Yuansheng Gao2, Paul M Vanhoutte3

  • 1Department of Pharmacology and Pharmacy, University of Hong Kong, 2/F, Laboratory Block, Li Ka Shing Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.

Handbook of Experimental Pharmacology
|January 2, 2016
PubMed
Summary

Inosine 3',5'-cyclic monophosphate (cIMP) acts as a second messenger in the vascular wall, regulating vascular contraction. This noncanonical cyclic nucleotide is synthesized in response to hypoxia and nitric oxide signaling.

Keywords:
HypoxiaInosine 3′,5′‐cyclic monophosphateMagnesium ionsRho kinaseSoluble guanylyl cyclase

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Area of Science:

  • Cardiovascular Biology
  • Molecular Signaling
  • Vascular Physiology

Background:

  • Traditionally, only adenosine 3",5 -cyclic monophosphate (cAMP) and guanosine 3",5 -cyclic monophosphate (cGMP) are recognized as vascular second messengers.
  • Other cyclic nucleotides exist in various tissues, but their roles in the vascular wall are less understood.

Purpose of the Study:

  • To investigate the role of inosine 3 ',5 '-cyclic monophosphate (cIMP) as a potential second messenger in the vascular wall.
  • To determine the synthesis pathway and functional significance of cIMP in porcine coronary arteries.

Main Methods:

  • Investigated the synthesis of cIMP by soluble guanylyl cyclase in response to hypoxia.
  • Examined the activation of soluble guanylyl cyclase by endothelium-derived nitric oxide.
  • Assessed the association of cIMP production with vascular contraction mediated by Rho kinase stimulation.

Main Results:

  • Hypoxia activates soluble guanylyl cyclase in porcine coronary arteries, leading to cIMP synthesis.
  • Endothelium-derived nitric oxide is involved in the activation of soluble guanylyl cyclase and subsequent cIMP production.
  • Increased cIMP levels correlate with augmented vascular contraction via Rho kinase activation.

Conclusions:

  • Inosine 3 ',5 '-cyclic monophosphate (cIMP) meets the criteria to be considered a second messenger in the vascular wall.
  • cIMP plays a role in hypoxia-induced vascular responses and contraction.
  • Nitric oxide and Rho kinase signaling pathways are implicated in cIMP-mediated vascular effects.