Am. J. Respir. Crit. Care Med., Volume 159, Number 1, January 1999, 235-243

Bronchoprotector Properties of Calcitonin Gene-related Peptide in Guinea Pig and Human Airways
Effect of Pulmonary Inflammation

ALAIN CADIEUX, NATHALIE P. MONAST, FRANÇOIS POMERLEAU, ALAIN FOURNIER, and CHANTAL LANOUE

Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Sherbrooke; and INRS-Santé, University of Quebec, Pointe Claire, Quebec, Canada

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 µg/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 µg/kg)-induced bronchoconstriction (60% at 114 µg/kg). Similarly, CGRP (10⁹ to 10⁶ M) prevented in a concentration-dependent manner the contraction elicited by SP (5 × 10⁸ 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 10⁶ 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 (10⁶ M) reduced by more than 75% the extent of the contraction evoked by 10⁶ 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.

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