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 bronchocontrictors, 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 less than 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 less than 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.
Gatto
C
C
Department of Pediatrics, University of Minnesota, Minneapolis 55455.
Lussky
R C
RC
Erickson
L W
LW
Berg
K J
KJ
Wobken
J D
JD
Johnson
D E
DE
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001696:Biomechanical Phenomena; D001839:Bombesin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology
D009479:Neuropeptides; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D013373:Substance P; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D001839:Bombesin