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 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.
Cadieux
A
A
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, INRS-Santé, University of Quebec, Pointe Claire, Quebec, Canada.
Monast
N P
NP
Pomerleau
F
F
Fournier
A
A
Lanoue
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010047:Ovalbumin / Q000494:pharmacology; D011014:Pneumonia / Q000473:pathology / Q000503:physiopathology; D013373:Substance P / Q000494:pharmacology
D013373:Substance P; D002217:Carbachol; D010047:Ovalbumin; D015740:Calcitonin Gene-Related Peptide