Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guanylate cyclase from the rat renal medulla is found in both the soluble and particulate fractions of the cell. Sucrose density gradient centrifugation and gel filtration in H2O and D2O indicate that the enzyme from the soluble cell fraction has the following properties: S20w, 6.3 S; Stokes radius, 54 A; partial specific volume, 0.75 ml/g; mass, 154,000 daltons; f/fo, 1.4; axial ratio (prolate ellipsoid), 7. The addition of 0.1% Lubrol PX to this fraction activates the enzyme and changes thartial specific volume, 0.74 ml/g; mass, 148,000 daltons; f/fo, 1.6; axial ratio (prolate ellipsoid), 11. These findings show that detergent activates the enzyme by changing its conformation and not simply by dispersing nonsedimentable membrane fragments. The dimensions of this guanylate cyclase in detergent are very similar to those of detergent-solubilized adenylate cyclase from the same tissue (Neer, E.J. (1974) J. Biol. Chem. 249, 6527-6531). Guanylate cyclase can be solubilized from the particulate cell fraction with 1% Lubrol PX but has properties quite different from those of the guanylate cyclase in the soluble cell fraction. It is a large aggregate with a value of S20,w of about 10 S, Stokes radius of 65 A, and a mass of approximately 300,000 daltons. However, the peaks of guanylate cyclase activity in column effluents and sucrose density gradients are very broad indicating a mixture of different size proteins. The conditions used to solubilize guanylate cyclase from the particulate fraction also solubilize adenylate cyclase, and the two activities can be separated on the same sucrose gradient. Studies of this sort require a rapid, accurate guanylate cyclase assay. We have developed an assay for guanylate cyclase activity which meets these criteria by adapting the competitive protein binding assay for guanosine cyclic 3':5' monophosphate originally described by Murad et al. (Murad, F., Manganiello, V., and Vaughn, M. (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 736-739).
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PMID:Guanylate cyclase from the rat renal medulla. Physical properties and comparison with adenylate cyclase. 24 Aug 41

A role for the NO-cGMP pathway in mediating chemosensory activation of feeding is suggested by intense NADPH diaphorase staining observed in nerve fibers that project from sensory cells in the lips to the CNS and by the presence in the CNS of a NO-activated guanylyl cyclase. In preparations reduced to isolated lips and CNS, intracellular recordings were made from motoneurons driven by the interneurons of the central pattern generator (CPG) for feeding. Fictive feeding in such preparations can be recorded from these motoneurons following the application of sucrose to the lips. Sucrose activation of fictive feeding is inhibited by the NO scavenger hemoglobin, the NO synthase inhibitor N omega-Nitro-L-Arginine Methyl Ester (L-NAME) and by methylene blue, an inhibitor of guanylyl cyclase. Fictive feeding in isolated lip-CNS preparations can be activated without sucrose by superfusion of NO donor molecules such as SNAP and hydroxylamine and by the nonhydrolyzable analog of cGMP, 8-bromo-cGMP. The feeding CPG can also be activated centrally by depolarizing a modulatory interneuron, the slow oscillator (SO). When the CPG is activated in this way, fictive feeding is not susceptible to inhibition by hemoglobin, the most potent of the inhibitors of sucrose-activated fictive feeding. Behavioral experiments on intact snails confirm the findings from in vitro experiments and show that hemoglobin prevents feeding and methylene blue significantly delays the onset of feeding. These results indicate (1) that NO is a putative chemosensory transmitter in the snail L. stagnalis, (2) that the NO-cGMP pathway can mediate chemosensory activation of specific patterns of centrally generated behavior, (3) that NO is not involved in transmission within the central network of neurons responsible for the behavior, and more generally (4) that a freely diffusing and highly reactive gaseous signalling molecule can have restricted and specific behavioral functions.
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PMID:Behavioral role for nitric oxide in chemosensory activation of feeding in a mollusc. 747 16

Studies have provided evidence for the role of gap junctional intercellular communication in syncytial tissue function. This study tested the hypothesis that the vasodilating effects of nitric oxide (NO) rely on gap junctions. The effects of the gap junction inhibitors octanol (10(-4) mol/l) and heptanol (10(-3) mol/l) were examined on acetylcholine-, the NO-donor S-nitroso-N-acetyl-penicillamine (SNAP)-, and guanosine-3',5'-cyclic monophosphate (cGMP)-induced relaxation. In addition, we tested varying concentrations of the gap junction inhibitor sucrose on SNAP-induced relaxation in the presence and absence of methylene blue, an inhibitor of guanylate cyclase. Helical strips of rat thoracic aorta were placed in muscle baths for isometric force measurements. Tissues treated with SNAP and cGMP were denuded of endothelium. Tissues incubated in octanol and heptanol exhibited 4- to 7-fold rightward shifts in acetylcholine-induced and 6- to 15-fold rightward shifts in SNAP-induced relaxation. Both octanol and heptanol produced 2-fold rightward shifts in cGMP-induced relaxation, comparably less in magnitude than shifts produced in acetylcholine- and SNAP-induced relaxation. Sucrose (10(-2) to 10(-1) mol/l) produced a concentration-dependent rightward shift of up to 30-fold in relaxation to SNAP. Incubation with methylene blue (10(-6) mol/l) altered this rightward shift only slightly, indicating a possible cGMP-independent mechanism for NO. These findings support the hypothesis that NO-induced vasodilation, through both cGMP-dependent and -independent pathways, relies on gap junctional communication.
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PMID:Inhibition of nitric oxide-induced vasodilation by gap junction inhibitors: a potential role for a cGMP-independent nitric oxide pathway. 886 45