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

Abstract

Calcitonin gene-related peptide (CGRP), a neuropeptide released from sensory nerves during axonal reflexes, has strong bronchoprotector properties in rat isolated airways. In this study, we examined this ability of CGRP to prevent agonist-induced contraction in guinea pig and human airways and determined whether inflammatory reaction affects its function. CGRP administered intravenously (0.38 to 114 microgram/kg) in anesthesized guinea pig had no effect per se on airway resistance but caused a dose-related inhibition of substance P (SP; 13.5 microgram/kg)-induced bronchoconstriction (60% at 114 microgram/kg). Similarly, CGRP (10(-)9 to 10(-)6 M) prevented in a concentration-dependent manner the contraction elicited by SP (5 x 10(-)8 M) in guinea pig isolated main bronchi and parenchymal strips, the inhibition caused by CGRP being more pronounced in distal than in proximal airways (47 and 20%, respectively, at 10(-)6 M). The breaking effect of CGRP on SP-induced constriction was however significantly reduced (p < 0.05) in guinea pig actively sensitized 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 was observed in human isolated peripheral bronchi. CGRP (10(-)6 M) reduced by more than 75% the extent of the contraction evoked by 10(-)6 M of carbamylcholine and its protector effect was totally abolished in bronchi showing clear morphological manifestation of inflammatory reaction. It is concluded that CGRP acts as a potent bronchoprotector agent on both guinea pig and human airways but its ability to limit the extent of airway responsiveness is strongly impaired in inflammatory conditions.