Involvement of neurogenic inflammation in antigen-induced bronchoconstriction in guinea pigs.
The role of tachykinins released from sensory nerves in bronchoconstriction induced by antigen was studied in sensitized guinea pigs anesthetized with pentobarbital sodium and pretreated with atropine. The combination of NK2 (SR-48968) and NK1 (CP-96,345) tachykinin-receptor antagonists abolished the increase in total pulmonary resistance (RL) evoked by intravenous capsaicin but did not affect the response evoked by intravenous histamine. A small dose of aerosolized ovalbumin (OVA, 0.1%) produced a small increase in RL that was further increased and markedly prolonged by the neutral endopeptidase (NEP) inhibitor phosphoramidon; this bronchoconstrictor effect of OVA was markedly reduced by the NK2-receptor antagonist and was abolished by the combination of the NK1 and NK2-receptor antagonists together. When a larger dose of OVA (0.5%) was used, a maximal bronchoconstrictor response was obtained. Phosphoramidon did not potentiate this response significantly. The combination of NK1- and NK2-receptor antagonists blunted the response at 5 min only slightly but markedly attenuated the later (10-20 min) response. These results show that tachykinins released from sensory nerves play a significant role in antigen-induced bronchoconstriction in guinea pigs. This effect is exaggerated when the normal modulation of neuropeptides by NEP is inhibited and is mediated predominantly by NK2-receptor activation, with a smaller contribution by NK1 receptors.
Bertrand
C
C
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Geppetti
P
P
Graf
P D
PD
Foresi
A
A
Nadel
J A
JA
D000336:Aerosols; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007114:Immunization; D007249:Inflammation; D008168:Lung / Q000294:innervation / Q000503:physiopathology; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010880:Piperidines / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D000336:Aerosols; D001549:Benzamides; D001713:Biphenyl Compounds; D006020:Glycopeptides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018041:Receptors, Neurokinin-2; C073839:SR 48968; D001285:Atropine; D006632:Histamine; D010047:Ovalbumin; D002211:Capsaicin; C008890:phosphoramidon; C066892:CP 96345