Phosphodiesterase 3 and 5 and cyclic nucleotide-gated ion channel expression in rat trigeminovascular system.
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.
Kruse
Lars S
LS
Department of Neurology, Glostrup Hospital, Nordre Ringvej 57, Denmark. lsk@dcb-glostrup.dk
Sandholdt
Nicolai T H
NT
Gammeltoft
Steen
S
Olesen
Jes
J
Kruuse
Christina
C
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D001011:Aorta / Q000502:physiology; D001488:Basilar Artery / Q000502:physiology*; D002536:Cerebral Arteries / Q000502:physiology*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D017931:DNA Primers; D005786:Gene Expression Regulation; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000098:blood supply*
D017931:DNA Primers; D007473:Ion Channels; D012333:RNA, Messenger; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517290:Pde3a protein, rat; C517294:Pde3b protein, rat; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat