Novel alpha(1)-adrenoceptor antagonism by the fluroquinolone antibiotic trovafloxacin

Abstract

Trovafloxacin, a fluroquinolone antibiotic, was recently found to be an inhibitor of pannexin-1 channels through which ATP is released as "find-me" signals in apoptotic Jurkat cells. Our interest in the role of pannexin-1 channels in α1-adrenoceptor-mediated vasoconstriction led us to the novel finding reported here. Concentration-response curves to methoxamine and phenylephrine were competitively antagonised by trovafloxacin (1-30µM) with a pKB of 5.54 and 5.32, respectively, in rat mesenteric small arteries isolated for myography. In comparison, prazosin (1-10nM) antagonised methoxamine concentration-response curves with a pKB of 9.76. Trovafloxacin (1-30µM) had no effect on either the thr..