Kruse LS, Sandholdt NT, Gammeltoft S, Olesen J, Kruuse CPhosphodiesterase 3 and 5 and cyclic nucleotide-gated ion channel expression in rat trigeminovascular system. Neurosci Lett 404:202-207

Department of Neurology, Glostrup Hospital, Nordre Ringvej 57, Denmark.
Neuroscience Letters (Impact Factor: 2.03). 09/2006; 404(1-2):202-7. DOI: 10.1016/j.neulet.2006.05.045
Source: PubMed


Activation of the trigeminovascular pain signalling system appears involved in migraine pathophysiology. However, the molecular mechanisms are only partially known. Stimulation of cAMP and cGMP production as well as inhibition of their breakdown induce migraine-like headache. Additionally, migraine may be associated with mutations in ion channels. The aim of the present study was to describe the expression of phosphodiesterase 3 (PDE3) and 5 (PDE5) and cyclic nucleotide-gated ion channels (CNG) in cerebral arteries, meninges, and the trigeminal ganglion. mRNA for PDE and CNG was determined in the rat middle cerebral artery, basilar artery, trigeminal ganglion, and dura mater using real-time PCR. PDE and CNG proteins were identified using Western blot. For comparison, rat aorta and mesenteric artery were analysed. PDE3A, PDE3B, and PDE5A mRNA were detected in all tissues examined except for PDE3A mRNA in dura mater and the trigeminal ganglion. PDE5A and PDE3A protein expression was present in both cerebral and peripheral arteries, whereas PDE3B protein was present only in the cerebral arteries. The CNGA4 and B1 subunit mRNAs were detected in cerebral arteries and CNGA2 also in the mesenteric artery. CNGA2 and A3 proteins were found in cerebral arteries and dura and CNGA1, CNGA2 and CNGA3 in the trigeminal ganglion. In conclusion, PDE3A, PDE3B, PDE5A, and five CNG subunits were expressed in several components of the trigeminovascular system of the rat. This suggests that modulation of cAMP and cGMP levels by PDE and activation of CNG may play a role in trigeminovascular pain signalling leading to migraine headache.

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    • "There are three functional subunits CNGA1-A3. All these three subunits were reported to be expressed both in vascular endothelial cells and vascular smooth muscle cells [8], [9], [24]–[26]. Previous study also suggested that CNGA1 expression in vascular smooth muscle is very low, because RT-PCR could detect CNGA1 in cultured vascular smooth muscle cells but Western blot and in situ hybridization failed to detect CNGA1 in vascular tissues [9], [24]. In the present study, we found the expression of CNGA2 and A3, but not A1, in the protein lysates from rat vascular smooth muscle cell layers. "
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