Role of neurokinin receptors in the behavioral effect of intravesical antigen infusion in guinea pig bladder.
OBJECTIVE
To characterize a guinea pig behavior model of bladder pain due to intravesical antigen infusion and to determine the role of neurokinin receptor subtypes in mediating this behavior.


METHODS
The influence of subtype-selective neurokinin receptor antagonists on increased abdominal licking behavior in response to intravesical antigen infusion in guinea pigs immunized with ovalbumin (OA) was determined.


RESULTS
Intravesical OA infusion for 30 minutes induced a significantly greater frequency (about 3-fold) of abdominal licking behavior than during either the 30 minutes pre-challenge or post challenge saline infusions. Treatment with IP capsaicin 7 to 10 days before OA challenge abolished the intravesical antigen-induced behavior. IP injection of the NK1 receptor antagonist CP 99994 (10 mg./kg. or 30 mg./kg.), 30 minutes pretreatment, inhibited the increase in the average number of abdominal licks during antigen infusion. The 30 mg./kg., but not the 10 mg./kg. dose increased the percent of animals showing antinociceptive activity (defined as 4 or less abdominal licks during the antigen infusion). The NK2 receptor antagonist SR 48968 reduced the antigen-induced abdominal licking behavior at IP doses of 3 and 10 mg./kg. but was ineffective at 1 mg./kg. The NK3 receptor antagonist SB 235375 (30 mg./kg., IP) did not reduce this behavior.


CONCLUSIONS
These results suggest a role for activation of NK1 and NK2, but not NK3 receptors, by tachykinins released from capsaicin-sensitive nerves, in the increased abdominal licking behavior response of guinea pigs to intravesical antigen infusion.
Ruggieri
M R
MR
Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Filer-Maerten
S
S
Hieble
J P
JP
Hay
D W
DW
D000283:Administration, Intravesical; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D064729:Neurokinin-1 Receptor Antagonists; D010047:Ovalbumin / Q000276:immunology; D017699:Pelvic Pain / Q000139:chemically induced*; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects*
D000941:Antigens; D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C073839:SR 48968; D010047:Ovalbumin; D002211:Capsaicin