title: Protease-activated receptor 2 activation inhibits N-type Ca2+ currents in rat peripheral sympathetic neurons.
abstract: The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type Ca(2+) currents (I(Ca-N)) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated Ca(2+) currents (I(Ca)), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on I(Ca). This PAR-2-induced inhibition was almost completely prevented by ω-CgTx, a potent N-type Ca(2+) channel blocker, suggesting the involvement of N-type Ca(2+) channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited I(Ca-N) in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ω-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type Ca(2+) channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type Ca(2+) channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals.
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Duck-Sun
authors.initials: DS
authors.lastname: Ahn
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Joeng
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Seungsoo
authors.initials: S
authors.lastname: Chung
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000201:enzymology*; D007022:Hypotension / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D020864:Calcium Channels, N-Type; D009842:Oligopeptides; D044464:Receptor, PAR-2; C497499:leucyl-arginyl-glycyl-isoleucyl-leucyl-serinamide; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide
keywords: N-type Ca2+ channel; celiac ganglion; hypotension; peripheral sympathetic output; protease-activated receptor 2