Abstract
Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been localized by immunohistochemistry to endothelial cells and adventitial nerves of blood vessels. HO-2 is also localized to neurons in autonomic ganglia, including the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the myenteric plexus of the intestine. Enzyme studies demonstrated that tin protoporphyrin-9 is a selective inhibitor of HO with approximately 10-fold selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble guanylyl cyclase. Inhibition of HO activity by tin protoporphyrin 9 reverses the component of endothelial-derived relaxation of porcine distal pulmonary arteries not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endothelial-derived relaxing activity. The similarity of NOS and HO-2 localizations and functions in blood vessels and the autonomic nervous system implies complementary and possibly coordinated physiologic roles for these two mediators.
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- Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
- Bredt D. S., Snyder S. H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682–685. doi: 10.1073/pnas.87.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bredt D. S., Snyder S. H. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci U S A. 1989 Nov;86(22):9030–9033. doi: 10.1073/pnas.86.22.9030. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bredt D. S., Snyder S. H. Nitric oxide, a novel neuronal messenger. Neuron. 1992 Jan;8(1):3–11. doi: 10.1016/0896-6273(92)90104-l. [DOI] [PubMed] [Google Scholar]
- Brüne B., Ullrich V. Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol Pharmacol. 1987 Oct;32(4):497–504. [PubMed] [Google Scholar]
- Chen G., Suzuki H., Weston A. H. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol. 1988 Dec;95(4):1165–1174. doi: 10.1111/j.1476-5381.1988.tb11752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen R. Y., Ross G., Chyu K. Y., Guth P. H. Role of L-arginine-derived nitric oxide in cholinergic dilation of gastric arterioles. Am J Physiol. 1993 Dec;265(6 Pt 2):H2110–H2116. doi: 10.1152/ajpheart.1993.265.6.H2110. [DOI] [PubMed] [Google Scholar]
- Cruse I., Maines M. D. Evidence suggesting that the two forms of heme oxygenase are products of different genes. J Biol Chem. 1988 Mar 5;263(7):3348–3353. [PubMed] [Google Scholar]
- Drummond G. S., Kappas A. Prevention of neonatal hyperbilirubinemia by tin protoporphyrin IX, a potent competitive inhibitor of heme oxidation. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6466–6470. doi: 10.1073/pnas.78.10.6466. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ewing J. F., Maines M. D. Rapid induction of heme oxygenase 1 mRNA and protein by hyperthermia in rat brain: heme oxygenase 2 is not a heat shock protein. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5364–5368. doi: 10.1073/pnas.88.12.5364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ewing J. F., Raju V. S., Maines M. D. Induction of heart heme oxygenase-1 (HSP32) by hyperthermia: possible role in stress-mediated elevation of cyclic 3':5'-guanosine monophosphate. J Pharmacol Exp Ther. 1994 Oct;271(1):408–414. [PubMed] [Google Scholar]
- Farrugia G., Irons W. A., Rae J. L., Sarr M. G., Szurszewski J. H. Activation of whole cell currents in isolated human jejunal circular smooth muscle cells by carbon monoxide. Am J Physiol. 1993 Jun;264(6 Pt 1):G1184–G1189. doi: 10.1152/ajpgi.1993.264.6.G1184. [DOI] [PubMed] [Google Scholar]
- Furchgott R. F., Jothianandan D. Endothelium-dependent and -independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light. Blood Vessels. 1991;28(1-3):52–61. doi: 10.1159/000158843. [DOI] [PubMed] [Google Scholar]
- Garland C. J., Plane F., Kemp B. K., Cocks T. M. Endothelium-dependent hyperpolarization: a role in the control of vascular tone. Trends Pharmacol Sci. 1995 Jan;16(1):23–30. doi: 10.1016/s0165-6147(00)88969-5. [DOI] [PubMed] [Google Scholar]
- Getchell M. L., Kulkarni-Narla A., Takami S., Albers K. M., Getchell T. V. Age-dependent phenotypic switching of mast cells in NGF-transgenic mice. Neuroreport. 1995 Jun 19;6(9):1261–1266. doi: 10.1097/00001756-199506090-00008. [DOI] [PubMed] [Google Scholar]
- Grundemar L., Johansson M. B., Ekelund M., Högestätt E. D. Haem oxygenase activity in blood vessel homogenates as measured by carbon monoxide production. Acta Physiol Scand. 1995 Feb;153(2):203–204. doi: 10.1111/j.1748-1716.1995.tb09852.x. [DOI] [PubMed] [Google Scholar]
- Ignarro L. J., Ballot B., Wood K. S. Regulation of soluble guanylate cyclase activity by porphyrins and metalloporphyrins. J Biol Chem. 1984 May 25;259(10):6201–6207. [PubMed] [Google Scholar]
- Ignarro L. J. Signal transduction mechanisms involving nitric oxide. Biochem Pharmacol. 1991 Feb 15;41(4):485–490. doi: 10.1016/0006-2952(91)90618-f. [DOI] [PubMed] [Google Scholar]
- Johnson R. A., Lavesa M., Askari B., Abraham N. G., Nasjletti A. A heme oxygenase product, presumably carbon monoxide, mediates a vasodepressor function in rats. Hypertension. 1995 Feb;25(2):166–169. doi: 10.1161/01.hyp.25.2.166. [DOI] [PubMed] [Google Scholar]
- Kovitz K. L., Aleskowitch T. D., Sylvester J. T., Flavahan N. A. Endothelium-derived contracting and relaxing factors contribute to hypoxic responses of pulmonary arteries. Am J Physiol. 1993 Oct;265(4 Pt 2):H1139–H1148. doi: 10.1152/ajpheart.1993.265.4.H1139. [DOI] [PubMed] [Google Scholar]
- Luo D., Vincent S. R. Metalloporphyrins inhibit nitric oxide-dependent cGMP formation in vivo. Eur J Pharmacol. 1994 May 17;267(3):263–267. doi: 10.1016/0922-4106(94)90149-x. [DOI] [PubMed] [Google Scholar]
- Marks G. S., Brien J. F., Nakatsu K., McLaughlin B. E. Does carbon monoxide have a physiological function? Trends Pharmacol Sci. 1991 May;12(5):185–188. doi: 10.1016/0165-6147(91)90544-3. [DOI] [PubMed] [Google Scholar]
- Meffert M. K., Haley J. E., Schuman E. M., Schulman H., Madison D. V. Inhibition of hippocampal heme oxygenase, nitric oxide synthase, and long-term potentiation by metalloporphyrins. Neuron. 1994 Nov;13(5):1225–1233. doi: 10.1016/0896-6273(94)90060-4. [DOI] [PubMed] [Google Scholar]
- Meffert M. K., Haley J. E., Schuman E. M., Schulman H., Madison D. V. Inhibition of hippocampal heme oxygenase, nitric oxide synthase, and long-term potentiation by metalloporphyrins. Neuron. 1994 Nov;13(5):1225–1233. doi: 10.1016/0896-6273(94)90060-4. [DOI] [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
- Morita T., Perrella M. A., Lee M. E., Kourembanas S. Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1475–1479. doi: 10.1073/pnas.92.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nagao T., Vanhoutte P. M. Hyperpolarization as a mechanism for endothelium-dependent relaxations in the porcine coronary artery. J Physiol. 1992 Jan;445:355–367. doi: 10.1113/jphysiol.1992.sp018928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nathan C. F., Hibbs J. B., Jr Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol. 1991 Feb;3(1):65–70. doi: 10.1016/0952-7915(91)90079-g. [DOI] [PubMed] [Google Scholar]
- Nathanson J. A., Scavone C., Scanlon C., McKee M. The cellular Na+ pump as a site of action for carbon monoxide and glutamate: a mechanism for long-term modulation of cellular activity. Neuron. 1995 Apr;14(4):781–794. doi: 10.1016/0896-6273(95)90222-8. [DOI] [PubMed] [Google Scholar]
- Prabhakar N. R., Dinerman J. L., Agani F. H., Snyder S. H. Carbon monoxide: a role in carotid body chemoreception. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1994–1997. doi: 10.1073/pnas.92.6.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenblum W. I. Endothelium-derived relaxing factor in brain blood vessels is not nitric oxide. Stroke. 1992 Oct;23(10):1527–1532. doi: 10.1161/01.str.23.10.1527. [DOI] [PubMed] [Google Scholar]
- Rotenberg M. O., Maines M. D. Isolation, characterization, and expression in Escherichia coli of a cDNA encoding rat heme oxygenase-2. J Biol Chem. 1990 May 5;265(13):7501–7506. [PubMed] [Google Scholar]
- Shibahara S., Müller R., Taguchi H., Yoshida T. Cloning and expression of cDNA for rat heme oxygenase. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7865–7869. doi: 10.1073/pnas.82.23.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sierra E. E., Nutter L. M. A microassay for heme oxygenase activity using thin-layer chromatography. Anal Biochem. 1992 Jan;200(1):27–30. doi: 10.1016/0003-2697(92)90271-8. [DOI] [PubMed] [Google Scholar]
- Stevens C. F., Wang Y. Reversal of long-term potentiation by inhibitors of haem oxygenase. Nature. 1993 Jul 8;364(6433):147–149. doi: 10.1038/364147a0. [DOI] [PubMed] [Google Scholar]
- Sun Y., Rotenberg M. O., Maines M. D. Developmental expression of heme oxygenase isozymes in rat brain. Two HO-2 mRNAs are detected. J Biol Chem. 1990 May 15;265(14):8212–8217. [PubMed] [Google Scholar]
- Taylor S. G., Weston A. H. Endothelium-derived hyperpolarizing factor: a new endogenous inhibitor from the vascular endothelium. Trends Pharmacol Sci. 1988 Aug;9(8):272–274. doi: 10.1016/0165-6147(88)90003-x. [DOI] [PubMed] [Google Scholar]
- Verma A., Hirsch D. J., Glatt C. E., Ronnett G. V., Snyder S. H. Carbon monoxide: a putative neural messenger. Science. 1993 Jan 15;259(5093):381–384. doi: 10.1126/science.7678352. [DOI] [PubMed] [Google Scholar]
- Zhuo M., Small S. A., Kandel E. R., Hawkins R. D. Nitric oxide and carbon monoxide produce activity-dependent long-term synaptic enhancement in hippocampus. Science. 1993 Jun 25;260(5116):1946–1950. doi: 10.1126/science.8100368. [DOI] [PubMed] [Google Scholar]