Effects of intravesical instillation of ATP on rat bladder primary afferent activity and its relationship with capsaicin-sensitivity.
OBJECTIVE
Previous studies have suggested that ATP has a role in mechano-afferent transduction, at least partly mediated by nerves other than capsaicin (Cap)-sensitive nerves. We investigated the direct effect of ATP on single fiber activity (SFA) of the primary bladder afferent nerves and its relationship with Cap-sensitivity.


METHODS
Female Sprague-Dawley rats were used. On the basis of conduction velocities, SFA was grouped as Aδ- or C-fibers. First, SFA and intravesical pressure were measured during filling as the baseline. Then, Cap (10(-5) M) was instilled intravesically and the SFA response was monitored. To desensitize Cap-sensitive nerves, resiniferatoxin (RTX) (10(-6) M) was administered intravesically, and then Cap was again administered to confirm the desensitization effect. Thereafter, ATP (10(-3) M) or its vehicle was instilled intravesically and another filling cycles recorded.


RESULTS
Thirty-two single afferent fibers were discriminated. Aδ-fibers did not respond to intravesical instillation of Cap, RTX or ATP. Based on Cap-sensitivity, C-fibers could be divided into two subtypes: Cap-sensitive (n=8) and Cap-insensitive (n=16). In the Cap-sensitive C-fibers, the response to bladder filling mostly disappeared after RTX desensitization, no matter if the bladder was filled with vehicle or ATP. On the other hand, in the Cap-insensitive C-fibers, even after RTX-treatment, the response was preserved and more enhanced when the bladder was filled with ATP compared to vehicle.


CONCLUSIONS
Mechanosensitive bladder afferents can be classified as (1) Aδ-fibers, (2) Cap-insensitive, and (3) Cap-sensitive C-fibers. The activation of the bladder afferents induced by intravesical application of ATP is mediated mainly through Cap-insensitive C-fibers.
Aizawa
Naoki
N
Department of Urology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Igawa
Yasuhiko
Y
Andersson
Karl-Erik
KE
Iijima
Kazuyoshi
K
Nishizawa
Osamu
O
Wyndaele
Jean-Jacques
JJ
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D000283:Administration, Intravesical; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D009498:Neurotoxins / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology
D004224:Diterpenes; D009498:Neurotoxins; D018689:Sensory System Agents; D000255:Adenosine Triphosphate; C024353:resiniferatoxin; D002211:Capsaicin