Abstract
Soluble guanylate cyclase (sGC), the receptor for nitric oxide, is a heterodimer consisting of alpha and beta subunits. We investigated the mRNA species for the alpha(1) subunit in human brain, heart, artery and immortalized B-lymphocytes. Three mRNA species were identified in these tissues. The major mRNA species contained the full expression sequence of the alpha(1) subunit. Two other types of mRNA were detected in which 5' sequences were deleted by splicing (506-590 and 412-590). Each of these deletions included the predicted translation start site, indicating that translation of these two alternatively spliced RNA species does not result in the production of full-length alpha(1) subunits. The relative amounts of the two mRNA species with deletions of the translation start site differed significantly between cell lines of immortalized B-lymphocytes from different individuals. sGC enzymic activity was significantly decreased in cellular extracts from cell lines with high proportions of mRNA species containing the deletion 506-590 when compared with extracts from cell lines that contained mostly mRNA without this deletion.
Full Text
The Full Text of this article is available as a PDF (168.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Behrends S., Harteneck C., Schultz G., Koesling D. A variant of the alpha 2 subunit of soluble guanylyl cyclase contains an insert homologous to a region within adenylyl cyclases and functions as a dominant negative protein. J Biol Chem. 1995 Sep 8;270(36):21109–21113. doi: 10.1074/jbc.270.36.21109. [DOI] [PubMed] [Google Scholar]
- Cardillo C., Kilcoyne C. M., Cannon R. O., 3rd, Panza J. A. Attenuation of cyclic nucleotide-mediated smooth muscle relaxation in blacks as a cause of racial differences in vasodilator function. Circulation. 1999 Jan 5;99(1):90–95. doi: 10.1161/01.cir.99.1.90. [DOI] [PubMed] [Google Scholar]
- Chhajlani V., Frändberg P. A., Ahlner J., Axelsson K. L., Wikberg J. E. Heterogeneity in human soluble guanylate cyclase due to alternative splicing. FEBS Lett. 1991 Sep 23;290(1-2):157–158. doi: 10.1016/0014-5793(91)81248-7. [DOI] [PubMed] [Google Scholar]
- Dean A. D., Vehaskari V. M., Ritter D., Greenwald J. E. Distribution and regulation of guanylyl cyclase type B in the rat nephron. Am J Physiol. 1996 Feb;270(2 Pt 2):F311–F318. doi: 10.1152/ajprenal.1996.270.2.F311. [DOI] [PubMed] [Google Scholar]
- Freedman J. E., Loscalzo J., Benoit S. E., Valeri C. R., Barnard M. R., Michelson A. D. Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis. J Clin Invest. 1996 Feb 15;97(4):979–987. doi: 10.1172/JCI118522. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giddings S. J., Carnaghi L. Rat insulin II gene expression by extraplacental membranes. A non-pancreatic source for fetal insulin. J Biol Chem. 1989 Jun 5;264(16):9462–9469. [PubMed] [Google Scholar]
- Giuili G., Scholl U., Bulle F., Guellaën G. Molecular cloning of the cDNAs coding for the two subunits of soluble guanylyl cyclase from human brain. FEBS Lett. 1992 Jun 8;304(1):83–88. doi: 10.1016/0014-5793(92)80594-7. [DOI] [PubMed] [Google Scholar]
- Harteneck C., Wedel B., Koesling D., Malkewitz J., Böhme E., Schultz G. Molecular cloning and expression of a new alpha-subunit of soluble guanylyl cyclase. Interchangeability of the alpha-subunits of the enzyme. FEBS Lett. 1991 Nov 4;292(1-2):217–222. doi: 10.1016/0014-5793(91)80871-y. [DOI] [PubMed] [Google Scholar]
- Huang P. L., Huang Z., Mashimo H., Bloch K. D., Moskowitz M. A., Bevan J. A., Fishman M. C. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature. 1995 Sep 21;377(6546):239–242. doi: 10.1038/377239a0. [DOI] [PubMed] [Google Scholar]
- Lopez M. J., Wong S. K., Kishimoto I., Dubois S., Mach V., Friesen J., Garbers D. L., Beuve A. Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide. Nature. 1995 Nov 2;378(6552):65–68. doi: 10.1038/378065a0. [DOI] [PubMed] [Google Scholar]
- Moro M. A., Russel R. J., Cellek S., Lizasoain I., Su Y., Darley-Usmar V. M., Radomski M. W., Moncada S. cGMP mediates the vascular and platelet actions of nitric oxide: confirmation using an inhibitor of the soluble guanylyl cyclase. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1480–1485. doi: 10.1073/pnas.93.4.1480. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nathan C., Xie Q. W. Nitric oxide synthases: roles, tolls, and controls. Cell. 1994 Sep 23;78(6):915–918. doi: 10.1016/0092-8674(94)90266-6. [DOI] [PubMed] [Google Scholar]
- Olson L. J., Knych E. T., Jr, Herzig T. C., Drewett J. G. Selective guanylyl cyclase inhibitor reverses nitric oxide-induced vasorelaxation. Hypertension. 1997 Jan;29(1 Pt 2):254–261. doi: 10.1161/01.hyp.29.1.254. [DOI] [PubMed] [Google Scholar]
- Panza J. A., Quyyumi A. A., Brush J. E., Jr, Epstein S. E. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990 Jul 5;323(1):22–27. doi: 10.1056/NEJM199007053230105. [DOI] [PubMed] [Google Scholar]
- Papapetropoulos A., Cziraki A., Rubin J. W., Stone C. D., Catravas J. D. cGMP accumulation and gene expression of soluble guanylate cyclase in human vascular tissue. J Cell Physiol. 1996 May;167(2):213–221. doi: 10.1002/(SICI)1097-4652(199605)167:2<213::AID-JCP4>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
- Schmidt H. H., Walter U. NO at work. Cell. 1994 Sep 23;78(6):919–925. doi: 10.1016/0092-8674(94)90267-4. [DOI] [PubMed] [Google Scholar]
- Stein C. M., Lang C. C., Nelson R., Brown M., Wood A. J. Vasodilation in black Americans: attenuated nitric oxide-mediated responses. Clin Pharmacol Ther. 1997 Oct;62(4):436–443. doi: 10.1016/S0009-9236(97)90122-3. [DOI] [PubMed] [Google Scholar]
- Wedel B., Harteneck C., Foerster J., Friebe A., Schultz G., Koesling D. Functional domains of soluble guanylyl cyclase. J Biol Chem. 1995 Oct 20;270(42):24871–24875. doi: 10.1074/jbc.270.42.24871. [DOI] [PubMed] [Google Scholar]
- Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]
- Yuen P. S., Doolittle L. K., Garbers D. L. Dominant negative mutants of nitric oxide-sensitive guanylyl cyclase. J Biol Chem. 1994 Jan 14;269(2):791–793. [PubMed] [Google Scholar]
- Zabel U., Weeger M., La M., Schmidt H. H. Human soluble guanylate cyclase: functional expression and revised isoenzyme family. Biochem J. 1998 Oct 1;335(Pt 1):51–57. doi: 10.1042/bj3350051. [DOI] [PMC free article] [PubMed] [Google Scholar]