Defining the Phosphodiesterase Superfamily Members in Rat Brain Microvessels

Overview

Journal ACS Chem Neurosci

Publisher American Chemical Society

Specialty Neurology

Date 2012 Aug 4

PMID 22860158

Citations 6

Authors

Zhen He

Li Cui

Tucker A Patterson

Merle G Paule

Affiliations

Soon will be listed here.

Abstract

Eleven phosphodiesterase (PDE) families are known, each having several different isoforms and splice variants. Recent evidence indicates that expression of individual PDE family members is tissue-specific. Little is known concerning detailed PDE component expression in brain microvessels where the blood-brain-barrier and the local cerebral blood flow are thought to be regulated by PDEs. The present study attempted to identify PDE family members that are expressed in brain microvessels. Adult male F344 rats were sacrificed and blocks of the cerebral cortex and infratentorial areas were dissected. Microvessels were isolated using a filtration method, and total RNA was extracted. RNA quality and quantity were determined using an Agilent bioanalyzer. The isolated cortical and infratentorial microvessel total RNA amounts were 2720 ± 750 ng (n = 2) and 250 ± 40 ng (n = 2), respectively. Microarrays with 22 000 transcripts demonstrated that there were 16 PDE transcripts in the PDE superfamily, exhibiting quantifiable density in the microvessels. An additional immunofluorescent study verified that PDE4D (cAMP-specific) and PDE5A (cGMP-specific) were colocalized with RECA-1 (an endothelial marker) in the cerebral cortex using both F344 rats and Sprague-Dawley rats (n = 3-6/strain). In addition, PDE4D and PDE5A were found to be colocalized with alpha-smooth muscle actin which delineates cerebral arteries and arterioles as well as pericytes. In conclusion, a filtration method followed by microarray analyses allows PDE components to be identified in brain microvessels, and confirmed that PDE4D and PDE5A are the primary forms expressed in rat brain microvessels.

Citing Articles

Transcriptional profile of the rat cardiovascular system at single-cell resolution.

Arduini A, Fleming S, Xiao L, Hall A, Akkad A, Chaffin M Cell Rep. 2024; 44(1):115091.

PMID: 39709602 PMC: 11781962. DOI: 10.1016/j.celrep.2024.115091.

Transcriptional profile of the rat cardiovascular system at single cell resolution.

Arduini A, Fleming S, Xiao L, Hall A, Akkad A, Chaffin M bioRxiv. 2023; .

PMID: 38014050 PMC: 10680727. DOI: 10.1101/2023.11.14.567085.

A negative allosteric modulator of PDE4D enhances learning after traumatic brain injury.

Titus D, Wilson N, Alcazar O, Calixte D, Dietrich W, Gurney M Neurobiol Learn Mem. 2018; 148:38-49.

PMID: 29294383 PMC: 5844849. DOI: 10.1016/j.nlm.2017.12.008.

A Working Module for the Neurovascular Unit in the Sexually Dimorphic Nucleus of the Preoptic Area.

He Z, Cui L, Ferguson S, Paule M Mol Neurobiol. 2017; 55(1):156-163.

PMID: 28840477 DOI: 10.1007/s12035-017-0729-6.

Dissecting gene expression at the blood-brain barrier.

Huntley M, Bien-Ly N, Daneman R, Watts R Front Neurosci. 2014; 8:355.

PMID: 25414634 PMC: 4222230. DOI: 10.3389/fnins.2014.00355.

References

Faraci F, Sobey C . Role of soluble guanylate cyclase in dilator responses of the cerebral microcirculation. Brain Res. 1999; 821(2):368-73. DOI: 10.1016/s0006-8993(99)01110-5. View

Pelligrino D, Wang Q . Cyclic nucleotide crosstalk and the regulation of cerebral vasodilation. Prog Neurobiol. 1998; 56(1):1-18. DOI: 10.1016/s0301-0082(98)00009-4. View

He Z, Yang S, Naritomi H, Yamawaki T, Liu Q, King M . Definition of the anterior choroidal artery territory in rats using intraluminal occluding technique. J Neurol Sci. 2000; 182(1):16-28. DOI: 10.1016/s0022-510x(00)00434-2. View

Kruuse C, Rybalkin S, Khurana T, Jansen-Olesen I, Olesen J, Edvinsson L . The role of cGMP hydrolysing phosphodiesterases 1 and 5 in cerebral artery dilatation. Eur J Pharmacol. 2001; 420(1):55-65. DOI: 10.1016/s0014-2999(01)01010-x. View

Stefanovich V . Cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP PDE) and cyclic 3',5'-guanosine monophosphate phosphodiesterase (cGMP PDE) in microvessels isolated from bovine cortex. Neurochem Res. 1979; 4(6):681-7. DOI: 10.1007/BF00964465. View

Wilson L, Elbatarny H, Crawley S, Bennett B, Maurice D . Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions. Proc Natl Acad Sci U S A. 2008; 105(36):13650-5. PMC: 2533244. DOI: 10.1073/pnas.0804738105. View

Houslay M, Milligan G . Tailoring cAMP-signalling responses through isoform multiplicity. Trends Biochem Sci. 1997; 22(6):217-24. DOI: 10.1016/s0968-0004(97)01050-5. View

Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T . Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med. 2009; 15(9):1031-7. DOI: 10.1038/nm.2022. View

Meschia J, Kissela B, Brott T, Brown Jr R, Worrall B, Beck J . The Siblings With Ischemic Stroke Study (SWISS): a progress report. Clin Med Res. 2006; 4(1):12-21. PMC: 1435656. DOI: 10.3121/cmr.4.1.12. View

10.

Minnear F, Johnson A, Malik A . Beta-adrenergic modulation of pulmonary transvascular fluid and protein exchange. J Appl Physiol (1985). 1986; 60(1):266-74. DOI: 10.1152/jappl.1986.60.1.266. View

11.

Barth A, Newell D, Nguyen L, Winn H, Wender R, Meno J . Neurotoxicity in organotypic hippocampal slices mediated by adenosine analogues and nitric oxide. Brain Res. 1997; 762(1-2):79-88. DOI: 10.1016/s0006-8993(97)00348-x. View

12.

Levin E . Are the terms blood-brain barrier and brain capillary permeability synonymous?. Exp Eye Res. 1977; 25 Suppl:191-9. DOI: 10.1016/s0014-4835(77)80017-1. View

13.

Castro L, Verde I, Cooper D, Fischmeister R . Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes. Circulation. 2006; 113(18):2221-8. PMC: 1877795. DOI: 10.1161/CIRCULATIONAHA.105.599241. View

14.

He Z, Cui L, Wu S, Li X, Simpkins J, McKinney M . Increased severity of acute cerebral ischemic injury correlates with enhanced stem cell induction as well as with predictive behavioral profiling. Curr Neurovasc Res. 2005; 1(5):399-409. DOI: 10.2174/1567202043361893. View

15.

Cui L, Pierce D, Light K, Melchert R, Fu Q, Kumar K . Sublethal total body irradiation leads to early cerebellar damage and oxidative stress. Curr Neurovasc Res. 2010; 7(2):125-35. PMC: 3637794. DOI: 10.2174/156720210791184880. View

16.

Lakics V, Karran E, Boess F . Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues. Neuropharmacology. 2010; 59(6):367-74. DOI: 10.1016/j.neuropharm.2010.05.004. View

17.

Bender A, Beavo J . Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev. 2006; 58(3):488-520. DOI: 10.1124/pr.58.3.5. View

18.

BARNARD J, Seibert A, Prasad V, Smart D, Strada S, Taylor A . Reversal of pulmonary capillary ischemia-reperfusion injury by rolipram, a cAMP phosphodiesterase inhibitor. J Appl Physiol (1985). 1994; 77(2):774-81. DOI: 10.1152/jappl.1994.77.2.774. View

19.

Cui L, Blanchard R, Cousins R . The permissive effect of zinc deficiency on uroguanylin and inducible nitric oxide synthase gene upregulation in rat intestine induced by interleukin 1alpha is rapidly reversed by zinc repletion. J Nutr. 2003; 133(1):51-6. DOI: 10.1093/jn/133.1.51. View

20.

Dolci S, Belmonte A, Santone R, Giorgi M, Pellegrini M, Carosa E . Subcellular localization and regulation of type-1C and type-5 phosphodiesterases. Biochem Biophys Res Commun. 2006; 341(3):837-46. DOI: 10.1016/j.bbrc.2006.01.035. View