Lactic acid-induced plasma protein extravasation in rat airways by stimulation of sensory nerves and NK1 receptor activation.
Locally applied lactic acid and capsaicin caused extravasation of Evans blue dye in trachea, main bronchi and nasal mucosa of anaesthetized rats. In animals pretreated with capsaicin to deplete sensory neuropeptides, the lactic acid response was abolished in main bronchi and highly reduced in trachea. Pretreatment with the NK1 receptor antagonist, RP 67580 (3 mg x kg-1 intravenously), markedly inhibited the lactic acid-induced extravasation at all levels; similar pretreatment with NK2 receptor antagonist, SR 48968 (0.5 mg x kg-1 intravenously), was ineffective. Locally applied ruthenium red (a transmembrane Ca2+ fluxes inhibitor), capsazepine (a capsacin receptor antagonist) and diclofenac intraperitoneally (a cyclooxygenase blocker) did not change the lactic acid effect, while the capsaicin response was only diminished in bronchi by local pretreatment with ruthenium red. In conclusion locally applied lactic acid in rat trachea and nasal cavity activated capsaicin sensitive sensory nerve endings producing plasma protein extravasation. This reaction was shown to be mediated by tachykinins acting on the NK1 receptor through a mechanism which appeared to be resistant to capsazepine and ruthenium red and independent of cyclooxygenase products. In comparison the effect of capsacin was partially ruthenium red-sensitive but not influenced by capsazepine.
Auberson
S
S
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Lundberg
J M
JM
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001798:Blood Proteins / Q000502:physiology*; D001980:Bronchi / Q000294:innervation / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D008297:Male; D009297:Nasal Mucosa / Q000294:innervation / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000294:innervation; D014132:Trachea / Q000294:innervation / Q000502:physiology
D001549:Benzamides; D001798:Blood Proteins; D007211:Indoles; D054833:Isoindoles; D007773:Lactates; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D019344:Lactic Acid; D005070:Evans Blue; C073839:SR 48968; D002211:Capsaicin