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

Abstract

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 wild-type 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 2 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.