Guanylyl cyclase receptors

Receptor Guanylyl Cyclases Generate the Second Messenger cGMP... 

A similar receptor guanylyl cyclase in the plasma membrane of intestinal epithelial cells is activated by an intestinal peptide, guanylin, which regulates Cl- secretion in the intestine. This receptor is also the target of a... 

Simpson P. J., Nighom A. and Morton D. B. (1999) Identification of a novel guanylyl cyclase that is related to receptor guanylyl cyclases but lacks extracellular and transmembrane domains. J. Biol. Chem. 274, 4440-4446. 

Leinders-Zufall T, Cockerham RE, Michalakis S, Biel M, Garbers DL, Reed RR, Zufall F, Munger SD (2007) Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium. Proc Natl Acad Sci USA 104 14507-14512 Liberies SD, Buck LB (2006) A second class of chemosensory receptors in the olfactory epithelium. Nature 442 645-650... 

Haghikia A, Mergia E, Friebe A et al (2007) Long-term potentiation in the visual cortex requires both nitric oxide receptor guanylyl cyclases. J Neurosci 27 818-823... 

Receptors linked to guanylyl cyclase and which catalyze the formation of guanosine triphosphate (GMP) to guanosine-3A -cychc monophosphate (cychc GMP) include those for atrial natriuretic factor (ANF) and endothehal-derived relaxing factor (EDRF), mediating vasodilatation, and nitric oxide [10102 3-9], NO, or a clearly related derivative. 

Guanylyl cyclases (GC) are a family of enzymes (EC 4.6.1.2) that catalyse the formation of the second messenger cyclic GMP (cGMP) from guanosine triphosphate (GTP). GCs are subdivided in soluble GCs and GCs that are membrane-bound and linked to a receptor. Activation occurs by nitric oxide (NO) and pqrtide hormones, respectively [1,2]. 

Mergia E, Friebe A, Dangel O et al (2006) Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system. J Clin Invest 116 1731-1737... 

II Receptors with intrinsic guanylyl cyclase activity... 

Activation of brain H receptors also stimulates cGMP synthesis [19]. Outside the brain, histamine is known to relax vascular smooth muscle by activation of endothelial H receptors, thereby increasing endothelial Ca2+ concentrations and stimulating the synthesis and release of nitric oxide. The latter, a diffusible agent, then activates the smooth muscle guanylyl cyclase [30]. Although less is known about these mechanisms in the CNS, there is evidence that brain H receptor activation can produce effects that depend on guanylyl cyclase activity [19]. 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

Membrane-bound forms of guanylyl cyclase act as plasma membrane receptors 368... 

Yuen, P. and Garbers, D. L. Guanylyl cyclase-linked receptors. Physiol. Rev. 75 865-885,1995. 

Kuhn, M. Structure, regulation and function of mammalian membrane guanylyl cyclase receptors, with a focus on guanylyl cyclase-A. Circ. Res. 93 700-709, 2003. 

Voltage-dependent Na+, K+, Ca2+ channels Ca2+-dependent potassium channels Enzymes and other proteins involved in the regulation of second messengers G proteins Phospholipases Adenylyl cyclases Guanylyl cyclases Phosphodiesterases IP3 receptor Protein kinases... 

The G a-subunit is critical to perpetuating the GPCR signal because it is the free a- and Py-subunits that activate effector proteins and ion channels, such as AC, guanylyl cyclase, phospholipases C and A, Ca and K+ channels (74). For example, while the activated G a tends to activate AC (75,76), the G-a tends to inhibit AC, and activated G a tends to activate phospholipase C-P (44,77). Variations in receptor structure can change the rate at which these G protein subunits are liberated. Enhanced or diminished receptor signaling can result from the disruption of these processes at any step. 

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