BRADYKININ EXCITES RAT SYMPATHETIC NEURONS BY INHIBITION OF M CURRENTTHROUGH A MECHANISM INVOLVING B-2 RECEPTORS AND G(ALPHA-Q 11)/

Bradykinin (BK) is a peptide mediator released in inflammation that po tently excites sympathetic neurons. We have studied the mechanism of t his excitation in dissociated rat sympathetic neurons and found that a t low nanomolar (EC(50) = (1.9 nM) concentrations, BK inhibited the M- type K+ current IK(M). Studies with the selective antagonist Hoe140 re vealed that this effect was mediated via the B-2 receptor subtype, and mRNA encoding this receptor was identified in these neurons by RT-PCR . I-K(M) inhibition was unaffected by Pertussis toxin or microinjectio n of antibodies to G(ao) but was selectively inhibited by microinjecti on of antibodies to Go(aq/11). Thus, BK is the most potent M current i nhibitor yet described in mammalian neurons, and BK inhibition of M cu rrent is mediated by a G protein pathway similar to that activated by muscarinic acetylchaline receptors.