Airway responses to capsaicin in guinea pigs: role of NK-1 and NK-2 neurokinin receptors.
The role of NK-1 and NK-2 receptors on the pulmonary response to capsaicin in guinea pigs was evaluated using intravenous infusion of selective nonpeptide antagonists of NK 1 (CP 96345, 300 nmol/kg, and SR 140333, 300 nmol/kg) and NK-2 (SR 48968, 100 nmol/kg) neurokinin receptors. Maximal values of pulmonary dynamic elastance (Edyn) and pulmonary resistance (RL) after capsaicin infusion were significantly lower in the presence of SR 48968 (p < .005). Morphometric analysis of lungs obtained by quick-freezing showed significant attenuation of airway contraction and peribronchiolar edema formation in the presence of NK-2 antagonist (p < .001). When compared to guinea pigs that received only capsaicin, animals that received SR 140333 or CP 96345 showed lower values of Edyn, RL, airway contraction, and peribronchiolar edema, but only the difference in Edyn values was significant. The combination of NK-1 and NK-2 antagonists was not more effective than NK-2 antagonist alone in attenuating capsaicin effects. The results suggest that airway effects of capsaicin are mainly mediated by activation of NK-2 receptors although NK-1 receptors may also play a role.
Vieira
J E
JE
Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Brazil.
Warth
M do P
Mdo P
Leme
A S
AS
Maldonado
E A
EA
King
M
M
Saldiva
P H
PH
Martins
M A
MA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects; D002211:Capsaicin / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000648:ultrastructure*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D014132:Trachea / Q000187:drug effects* / Q000648:ultrastructure*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001549:Benzamides; D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C085215:SR 140333; C073839:SR 48968; D002211:Capsaicin; C066892:CP 96345