Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH United Kingdom
*Address for Corresponding Author
Cardiovascular Research Group, School of Biomedical Sciences,
University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH United Kingdom
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 is 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 suggests 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.
Keywords: Noradrenaline, pannexins, porcine splenic artery, purinoceptor agonists, vasculature