Activation of splanchnic and pelvic colonic afferents by bradykinin in mice.
BACKGROUND
Lumbar splanchnic (LSN) and sacral pelvic (PN) nerves convey different mechanosensory information from the colon to the spinal cord. Here, we determined whether these pathways differ also in their chemosensitivity to bradykinin.


METHODS
Using a novel in vitro mouse colon preparation, serosal afferents were recorded from the LSN and PN and distinguished based on their mechanosensitivity to von Frey filaments (70-4000 mg) and insensitivity to colonic stretch (1-5 g) or fine mucosal stroking (10 mg). Bradykinin was applied into a ring around mechanoreceptive fields.


RESULTS
The LSN and PN afferents had different dynamic responses to mechanical stimuli: PN afferents required lower intensity stimuli, evoked larger responses, and displayed more maintained responses than LSN afferents. Bradykinin (1 micromol L-1) excited 66% (27 of 41) of LSN afferents. Responses to probing were potentiated after bradykinin. The concentration-dependent (EC50: 0.16 micromol L-1) response was reversed by the B2-receptor antagonist HOE-140 (10 nmol L-)). Twelve bradykinin responsive afferents were mechanically insensitive. More LSN serosal afferents responded to bradykinin than PN afferents (11%, P<0.001) , with larger responses (P<0.05). No mechanically insensitive PN afferents were recruited by bradykinin.


CONCLUSIONS
Bradykinin potently stimulates most splanchnic serosal afferents via B2-receptors, but few pelvic afferents. Mechanically insensitive afferents recruited by bradykinin are exclusive to the LSN.
Brierley
S M
SM
Nerve-Gut Research Laboratory, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia. stuart.brierley@adelaide.edu.au
Jones
R C W
RC
Xu
L
L
Gebhart
G F
GF
Blackshaw
L A
LA
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D003106:Colon / Q000294:innervation* / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000502:physiology; D010388:Pelvis / Q000294:innervation* / Q000502:physiology*; D010812:Physical Stimulation; D018002:Receptors, Bradykinin / Q000819:agonists / Q000187:drug effects; D013153:Splanchnic Nerves / Q000502:physiology*
D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin; C065679:icatibant; D001920:Bradykinin