Cyclic GMP accumulation

SCHROEDER, H., LEITMAN, D. C., Hayward, L. D., Bennett, B. M., Murphy, F., Cultured rat lung fibroblasts as a model for organic nitrate-induced cyclic GMP accumulation and activation of guanylate cyclase. J. Appl. Cardiol. 2 (1987), p. 301-311... 

Bennett, B. M., MacDonald, B. J., Nigam, R., Long, P. G., Simon, W. C., Inhibition of nitrovasodilator- and acetylcholine-induced relaxation and cyclic GMP accumulation by the cytochrome P450 substrate 7-ethoxyresorufin. Can. J. Physiol. Pharmacol. 70 (1992), p. 1297-1303... 

B. M. Bennett, D. C. Leitman, H. Schroder, J. H. Kawamoto, K. Nakatsu, F. Murad, Relationship Between Biotransformation of Glyceryl Trinitrate and Cyclic GMP Accumulation in Various Cultured Cell Lines , J. Pharmacol. Exp. Ther. 1989, 250, 316-323. 

The moderately selective PDE type V-inhibitor sildenafil (Viagra ) has been introduced in the treatment of erectile dysfunction. On the basis of cyclic GMP accumulation sildenafil is claimed to be a selective vasodilator in erectile tissues in the penis because of the high concentration of PDE type V in this region. Several of its adverse reactions (headache, flush, hypotension) reflect its vasodilator actions in other vascular beds than that of the penis. The drug will not be further discussed here. 

Ignarro, L. J., Burke, T. M., Wood, K. S., Wolin, M. S., and Kadowitz, P. J. (1984b). Association between cyclic GMP accumulation and acetylcholine-elicited telaxation of bovine intrapulmonary artery.). Pharmacol. Exp. Ther. 228, 682-690. 

Mellion, B. T., Ignarro, L. J., Myers, C. B., Ohlstein, E. H., Ballot, B. A., Hyman, A. L., and Kadowitz, P. J. (1983). Inhibition of human platelet aggregation by S-nitrosothiols. Heme-dependent activation of soluble guanylate cyclase and stimulation of cyclic GMP accumulation. Mol. Pharmacol. 23, 653-664. 

Initial biochemical studies indicate that agonist binding was regulated by guanyl nucleotides, implying that the receptor belongs to the superfamily of receptors coupled to G proteins. In addition, various intracellular responses were found to be associated with Hi-receptor stimulation inositol phosphate release, increase in Ca2+ fluxes, cyclic AMP or cyclic GMP accumulation in whole cells and arachidonic acid release [1],... 

MolinaCR,AndresenJW,RapoportRM, Waldman S, Murad F. 1987. Effect of in vivo nitroglycerin therapy on endothelium-dependent and -independent vascular relaxation and cyclic GMP accumulation in rat aorta. J. Cardiovasc. Pharmacol. 10 371-78... 

M., and Konijn, T. M. (1977) Cyclic AMP and folic acid stimulated cyclic GMP accumulation in Dictyostelium discoideum. FEES Lett. 79, 331-336. 

Minneman, K. P., and Iversen, L. L., 1976, Enkephalin and opiate narcotics increase cyclic GMP accumulation in slices of rat neostriatum. Nature 262 313. 

O Dea, R. F., and Zatz, M., 1976, Catecholamine-stimulated cyclic GMP accumulation in the rat pineal Apparent presynaptic site of action, Proc. Natl. Acad. Sci. USA 73 3398. 

Guanylate cyclase, the enzyme that catalyzes the biosynthesis of cyclic GMP from GTP, has been shown to be activated in rat-brain slices by HA, resulting in increased accumulation of cyclic GMP . In addition, HA was demonstrated to possess vasodila-... 

Cyclic GMP decreases basal and stimulated concentrations of intracellular Ca (Nakashima et al, 1986 Johansson and Haynes, 1992). A number of Ca handling systems have been identified in platelets including receptor operated channels, passive leak, Ca -ATPase extrusion pump, the NaV Ca exchanger, Ca -accumulating ATPase pump of the dense tubular membrane (an intraplatelet membrane Ca store) and passive leakage and receptor operated Ca chatinels in the dense tubular membrane. In principle, all these... 

Chintala MS, Bernardino V, Chiu PJ (1994) Cyclic GMP but not cydic AMP prevents renal platdet accumulation after ischemia-reperftision in anesthetized rats. J Phannacol Exp Ther 271 1203-1208. 

Methylxanthines inhibit phosphodiesterase in many tissues, and theophylline is about six times as potent as caffeine [6]. The potentiation of drug effects by methylxanthines has often been interpreted as accumulation of cyclic AMP, but methylxanthines also promote the accumulation of cyclic GMP [37]. Methylxanthines also inhibit adenylate cyclase activity in some tissues, as, for example, the noradrenaline-stimulated adenylate cyclase activity in rat erythrocyte ghosts [38], the vasopressin-stimulated adenylate cyclase activity in toad bladder epithelium [39], the increase in cyclic AMP produced in brain slices by depolarising stimuli and by adenosine [40], and the adenylate cyclase activity in guinea-pig lung particles [41]. Both basal and glucagon-stimulated phosphorylase activity in rat liver slices are inhibited by theophylline [42]. However, methylxanthines also have pharmacological effects which are not related to inhibition of phosphodiesterase [43]. 

Dyphylline [l,3-dimethyl-7-(2, 3-dihydroxypropyl)xan-thine] and theophylline inhibit cyclic nucletide PDFs, thereby preventing breakdown of cyclic AMP and cyclic GMP to 5 -AMP and 5 -GMP, respectively. Inhibition of PDFs will lead to an accumulation of cAMP and cGMP, thereby increasing signal transduction through these pathways. The cyclic nucleotide PDFs are members of a superfamily of genetically distinct enzymes. Theophylline and related methylxanthines are relatively nonselective in the PDF subtypes they inhibit. 

Schini, V., Grant, N. J., Miller, R. C., and Takeda, K. (1989) Morphological characterization of cultured bovine aortic endothelial cells and the effects of atriopeptin II and sodium nitropmsside on cellular and extracellular accumulation of cyclic GMP Euk j. Cell Biol. 47,53-61. 

Descotes J (1992) Immunotoxicology of cadmium. In Nordberg GF, Herber RFM, Alessio L (eds) Cadmium in the human environment toxicity and carcinogenicity. Inti Agency Res Cancer, Lyon, France, pp 385-390 Donnelly TE (1978) Effects of zinc chloride on the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart. Biochim Biophys Acta 522 151-160 Dorian C, Gattone VH II, Klaassen CD (1992) Renal cadmium disposition and injuries as a result of accumulation of cadmium-metallothionein by the proximal convoluted tubules - a light microscopic autoradiography study with CdMT. Toxicol Appl Pharmacol 114 173-181... 

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