Expression of B-1 and B-2 bradykinin receptor mRNA and their functional roles in sympathetic ganglia and sensory dorsal root ganglia neurones from wild-type and B-2 receptor knockout mice

Bradykinin has been implicated in nociception and inflammation. To examine the relative significance of B-1 and B-2 bradykinin receptor subtypes in sympathetic and sensory ganglia, the electrophysiological effects of bradykinin analogues and the expression of receptor subtype mRNA 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 activated inward currents in dorsal root ganglia (DRG) neurones. Responses 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 inhibitor captopril, but not in DRG neurones. The up-regulation of responses to [des-Arg(10)]-kallidin and substance P were blocked by indomethacin and, thus, were dependent upon cyclo-oxygenase activity. The effects 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 receptor mRNA in interleukin treated SCG from B-1 knockout mice, no depolarizing effects of the B-1 receptor agonist [des-Arg(10)]-kallidin were observed. The successful elimination of bradykinin responses and B-2 mRNA in sympathetic and sensory ganglia from B-2 knockout mice, confirms that B-2 receptors are the predominant functional bradykinin receptor subtype in these tissues and that B-1 receptor mRNA is expressed in both sympathetic and sensory ganglia from these animals. (C) 1997 Elsevier Science Ltd.