Bronchoprotector properties of calcitonin gene-related peptide in guinea pig and human airways - Effect of pulmonary inflammation

Calcitonin gene-related peptide (CGRP), a neuropeptide released from sensor y nerves during axonal reflexes, has strong bronchoprotector properties in rat isolated airways. In this study, we examined this ability of CGRP to pr event agonist-induced contraction in guinea pig and human airways and deter mined whether inflammatory reaction affects its function. CGRP administered intravenously (0.38 to 114 mu g/kg) in anesthesized guinea pig had no effe ct per se on airway resistance but caused a dose-related inhibition of subs tance P (SP; 13.5 mu g/kg)-induced bronchoconstriction (60% at 114 mu g/kg) . Similarly, CGRP (10(-9) to 10(-6) M) prevented in a concentration-depende nt manner the contraction elicited by SP (5 x 10(-8) M) in guinea pig isola ted main bronchi and parenchymal strips, the inhibition caused by CGRP bein g more pronounced in distal than in proximal airways (47 and 20%, respectiv ely, at 10(-6) M). The breaking effect of CGRP on SP-induced constriction w as however significantly reduced (p < 0.05) in guinea pig actively sensitiz ed to ovalbumin (OA) and the loss in its potency was of similar magnitude ( >40%) whether it was administered in vivo or in vitro. A same phenomenon wa s observed in human isolated peripheral bronchi. CGRP (10-6 M) reduced by m ore than 75% the extent of the contraction evoked by 10(-6) M of carbamylch oline and its protector effect was totally abolished in bronchi showing cle ar morphological manifestation of inflammatory reaction. It is concluded th at CGRP acts as a potent bronchoprotector agent on both guinea pig and huma n airways but its ability to limit the extent of airway responsiveness is s trongly impaired in inflammatory conditions.