EXPRESSION OF B-1 AND B-2 BRADYKININ RECEPTOR MESSENGER-RNA AND THEIRFUNCTIONAL ROLES IN SYMPATHETIC-GANGLIA AND SENSORY DORSAL-ROOT GANGLIA NEURONS FROM WILD-TYPE AND B-2 RECEPTOR KNOCKOUT MICE

Bradykinin has been implicated in nociception and inflammation. To exa mine the relative significance of B-1 and B-2 bradykinin receptor subt ypes in sympathetic and sensory ganglia, the electrophysiological effe cts of bradykinin analogues and the expression of receptor subtype mRN A were examined in wild-type and ''B-2 knockout'' mice from which the B-2 receptor gene had been deleted. In wildtype mice the B-2 receptor agonist bradykinin depolarized superior cervical ganglia (SCG) and act ivated inward currents in dorsal root ganglia (DRG) neurones. Response s to the B-1 receptor agonist, [des-Arg(10)]-kallidin, were seen only in SCG that had been pre-treated with interleukins and the peptidase i nhibitor captopril, but not in DRG neurones. The up-regulation of resp onses to [des-Arg(10)]-kallidin and substance P were blocked by indome thacin and, thus, were dependent upon cyclo-oxygenase activity. The ef fects of bradykinin were abolished in SCG and DRG's from B-2 knockout mice and this was correlated with the absence of B-2 receptor mRNA in ganglia from these animals. However, despite the presence of B-1 recep tor mRNA in interleukin treated SCG from B-1 knockout mice, no depolar izing effects of the B-1 receptor agonist [des-Arg(10)]-kallidin were observed. The successful elimination of bradykinin responses and B-2 m RNA in sympathetic and sensory ganglia from B-2 knockout mice, confirm s that B-2 receptors are the predominant functional bradykinin recepto r subtype in these tissues and that B-1 receptor mRNA is expressed in both sympathetic and sensory ganglia from these animals. (C) 1997 Else vier Science Ltd.