Bradykinin excites rat sympathetic neurons by inhibition of M current through a mechanism involving B2 receptors and G alpha q/11.
Bradykinin (BK) is a peptide mediator released in inflammation that potently excites sympathetic neurons. We have studied the mechanism of this excitation in dissociated rat sympathetic neurons and found that at low nanomolar (EC50 = 0.9 nM) concentrations, BK inhibited the M-type K+ current IK(M). Studies with the selective antagonist Hoe140 revealed that this effect was mediated via the B2 receptor subtype, and mRNA encoding this receptor was identified in these neurons by RT-PCR. IK(M) inhibition was unaffected by Pertussis toxin or microinjection of antibodies to G alpha o but was selectively inhibited by microinjection of antibodies to G alpha q/11. Thus, BK is the most potent M current inhibitor yet described in mammalian neurons, and BK inhibition of M current is mediated by a G protein pathway similar to that activated by muscarinic acetylcholine receptors.
Wellcome Laboratory for Molecular Pharmacology, Department of Pharmacology, University College London, England.
S
S
Jones
D A
DA
Brown
G
G
Milligan
E
E
Willer
N J
NJ
Buckley
M P
MP
Caulfield
D000818:Animals; D001483:Base Sequence; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D017931:DNA Primers; D005091:Exons; D019204:GTP-Binding Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D018002:Receptors, Bradykinin / Q000096:biosynthesis / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000502:physiology*
D017931:DNA Primers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012333:RNA, Messenger; D018002:Receptors, Bradykinin; C065679:icatibant; D019204:GTP-Binding Proteins; D001920:Bradykinin