Evidence for the involvement of calcitonin gene-related peptide in the epithelium-dependent contraction of guinea-pig trachea in response to capsaicin.
Capsaicin (10(-9) to 10(-5) M) contracted guinea-pig tracheal strips. Epithelium-containing tracheal strips developed a maximum active tension which was significantly higher than that observed in epithelium-free strips. Anti-CGRP (calcitonin gene-related peptide) serum blocked the epithelium-dependent potentiation of the capsaicin-induced contraction in the intact tracheal strips, without affecting the response of the epithelium-free strips. This result suggests the occurrence of an epithelium-dependent release of CGRP. This same serum markedly reduced the contraction induced by exogenous rat CGRP in both intact and epithelium-free tracheal strips. In epithelium-free tracheal strips, capsaicin-induced contraction was abolished by spantide (10(-6) and 10(-5) M), a substance P antagonist, but, in intact tracheal strips, spantide did not abolish the capsaicin-induced contraction, showing that both CGRP and substance P release are directly induced by capsaicin. Moreover, the contractile responses to rat CGRP of intact tracheal strips from guinea pig suggest that CGRP itself might be able to release a contracting factor from the airway epithelium. Therefore, CGRP originating from the airway epithelium may play a major role in the control of airway smooth muscle tone.
Tschirhart
E
E
Laboratoire de Neuroimmunopharmacologie, Université Louis Pasteur-Strasbourg I, Illkirch, France.
Bertrand
C
C
Theodorsson
E
E
Landry
Y
Y
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D004848:Epithelium / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea / Q000502:physiology
D000906:Antibodies; D013373:Substance P; C042867:spantide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin