An examination into the function of pannexin in noradrenaline induced
vasoconstriction in porcine splenic artery
Abstract
Background: Pannexins are newly discovered proteins that were first
discovered by Panchin et al. in 2000. This aim of this work was to
examine the presence and function of pannexins in the porcine splenic
artery (PSA) in which α1A–adrenoceptors are present. Materials and
Methods: The involvement of pannexin channels was studied using several
pannexin inhibitors, i.e. mefloquine (a non-selective pannexin
inhibitor), probenecid (a selective pannexin-1 inhibitor at low
concentrations) and carbenoxolone (a selective pannexin-1 inhibitor).
Additionally, the involvement of ATP (via activation of P2
purinoceptors) in NA-induced contractile responses as well as
sympathetic nerve activation was examined using P2 purinoceptor
antagonists (PPADS and suramin). Results: Our data showed that both
pannexin-1 and pannexin-2 are present in the PSA. Mefloquine and
probenecid reduced the responses to both noradrenaline-induced
contractions and the frequency-dependent response curves generated to
sympathetic nerve stimulation, whereas carbenoxolone, suramin and PPADS
had no effect on responses to neither exogenous NA nor those caused by
activating the sympathetic nerves, arguing against the role of ATP in
mediating noradrenaline-induced responses in the PSA. This is because
mefloquine demonstrated non-selective inhibitory actions on contractile
responses since it was also shown to inhibit responses to 5-HT and
U46619 (the thromboxane mimetic). Conclusion: The present work therefore
provided evidence for the involvement of pannexin channels in conducting
responses to NA-induced α1-adrenoceptor-mediated vasoconstriction in
blood vessels in PSA, although great care must be taken in interpreting
this data on the basis of a lack of selectivity of the pharmacological
agents currently available as pannexin inhibitors