[en] The effects of calcitonin gene-related peptide (CGRP) (6 x 10(-8) M) on hemodynamics and on pulmonary microvascular permeability were investigated in isolated, perfused rabbit lungs by measuring the arterial, capillary and venous pressures and the capillary filtration coefficient (Kf,c). CGRP was administered alone or in combination with capsaicin (10(-4) M), acetylcholine (ACh) (10(-11) M to 10(-7) M), substance P (SP) (10(-10) M to 10(-6) M) and serotonin (10(-4) M). The influence of a specific antagonist of CGRP receptors, CGRP8-37 (10(-8) M), on the pulmonary edema induced by these mediators was also considered. CGRP had no direct effect on the vascular pressures or on Kf,c. Capsaicin and serotonin induced an increase in Kf,c of 271 +/- 49% and 676 +/- 147% of base line, respectively. ACh and SP also increased the microvascular permeability, in proportion to the concentration. The effects of capsaicin, ACh and SP have been related to the activation of neurokinin NK1 receptors. Co-administration of CGRP with capsaicin and ACh enhanced the increase in Kf,c induced by these two drugs. By contrast, when co-injected with SP, CGRP inhibited the Kf,c increase induced by 10(-8) M and 10(-7) M of SP (P < .05) and significantly decreased the arterial and capillary pressures. CGRP also partly prevented the pulmonary edema induced by serotonin (P < .05). Pretreatment with CGRP8-37 partly prevented the effects of capsaicin and ACh on Kf,c but bestowed no protection against SP-induced pulmonary edema. These data suggest that CGRP is co-released with SP from the C-fibers upon the action of capsaicin and ACh in the rabbit lung. Because CGRP potentiated the pulmonary edema induced in capsaicin and ACh, but decreased the effects of SP, we hypothesize that CGRP exerts a positive retro-control on the release of neuropeptides by these fibers but can attenuate their effects on the target cells.
Disciplines :
Pharmacy, pharmacology & toxicology Veterinary medicine & animal health
Author, co-author :
Delaunois, Annie ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Gustin, Pascal ; Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie
Ansay, Michel ; Université de Liège - ULiège > Services généraux (Faculté de médecine vétérinaire) > Relations académiques et scientifiques (Méd. vétérinaire)
Language :
English
Title :
Modulation of the acetylcholine- and substance P-induced pulmonary edema by calcitonin gene-related peptide in the rabbit.
Publication date :
1994
Journal title :
Journal of Pharmacology and Experimental Therapeutics
ISSN :
0022-3565
eISSN :
1521-0103
Publisher :
American Society for Pharmacology and Experimental Therapeutics, Bethesda, United States - Maryland