Calcitonin and CGRP block bombesin- and substance P-induced increases in airway tone

Calcitonin gene-related peptide (CGRP) and calcitonin (C) are two peptides that are cocontained and probably coreleased with the potent bronchoconstrictors, bombesin (B) and substance P (SP), within the lung. Although CGRP and C have a wide intrapulmonary distribution, their actions have not been well defined. By the use of a computerized lung mechanics analyzer, changes in response to 10-min infusions of these agents were measured in spontaneously breathing, anesthetized guinea pigs. Infusion of 0.3 nmol·kg^-1·min^-1 CGRP and 2 nmol·kg^-1·min^-1 C caused little change in lung mechanics. Infusion of 0.06 nmol·kg^-1·min^-1 B and 0.3 nmol·kg^-1·min^-1 SP caused a marked increase in inspiratory, expiratory, and total pulmonary resistance (RT), from base-line values (P < 0.02), with a maximal effect at 10 min postinfusion (PI) [RT = 326 ± 20% (SE) (B), 490 ± 73% (SP)]. Coinfusion of C or CGRP with B or SP at the above concentrations caused a marked reduction in SP - [RT = 189 ± 28% (C), 142 ± 16% (CGRP) at 10 min PI] and B - [RT = 157 ± 18% (C), 158 ± 10% (CGRP) at 10 min PI] induced changes in resistance (P < 0.015). The mode of action of C and CGRP is unknown, but these peptides may antagonize the effects of B and SP via autonomic pathways by interfering with B- or SP-induced changes in intracellular calcium concentrations or by increasing intracellular cAMP levels by binding to specific cellular receptors linked to adenylate cyclase.