Expression of B1 and B2 bradykinin receptor mRNA and their functional roles in sympathetic ganglia and sensory dorsal root ganglia neurones from wild-type and B2 receptor knockout mice.
Bradykinin has been implicated in nociception and inflammation. To examine the relative significance of B1 and B2 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 "B2 knockout" mice from which the B2 receptor gene had been deleted. In wild-type mice the B2 receptor agonist bradykinin depolarized superior cervical ganglia (SCG) and activated inward currents in dorsal root ganglia (DRG) neurones. Responses to the B1 receptor agonist, [des-Arg10]-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-Arg10]-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 B2 knockout mice and this was correlated with the absence of B2 receptor mRNA in ganglia from these animals. However, despite the presence of B1 receptor mRNA in interleukin treated SCG from B2 knockout mice, no depolarizing effects of the B1 receptor agonist [des-Arg10]-kallidin were observed. The successful elimination of bradykinin responses and B2 mRNA in sympathetic and sensory ganglia from B2 knockout mice, confirms that B2 receptors are the predominant functional bradykinin receptor subtype in these tissues and that B1 receptor mRNA is expressed in both sympathetic and sensory ganglia from these animals.
Seabrook
G R
GR
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
Bowery
B J
BJ
Heavens
R
R
Brown
N
N
Ford
H
H
Sirinathsinghi
D J
DJ
Borkowski
J A
JA
Hess
J F
JF
Strader
C D
CD
Hill
R G
RG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism*
D016207:Cytokines; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin