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.

Annals of the New York Academy of SciencesVolume 547, Issue 1 p. 532-533 Calcitonin and Calcitonin Gene-Related Peptide Block Bombesin- and Substance P- Induced Increases in Airway Resistance DANA E. JOHNSON, Corresponding Author DANA E. JOHNSON Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaAddress correspondence to Dana E. Johnson, M.D., Ph.D., Box 211, University Hospital, Harvard Street at East River Road, Minneapolis, MN 55455.Search for more papers by this authorRICHARD C. LUSSKY, RICHARD C. LUSSKY Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this authorLAURA W. ERICKSON, LAURA W. ERICKSON Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this authorJANE D. WOBKEN, JANE D. WOBKEN Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this authorKERRY J. BERG, KERRY J. BERG Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this authorCATHERINE GATTO, CATHERINE GATTO Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this author DANA E. JOHNSON, Corresponding Author DANA E. JOHNSON Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaAddress correspondence to Dana E. Johnson, M.D., Ph.D., Box 211, University Hospital, Harvard Street at East River Road, Minneapolis, MN 55455.Search for more papers by this authorRICHARD C. LUSSKY, RICHARD C. LUSSKY Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this authorLAURA W. ERICKSON, LAURA W. ERICKSON Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this authorJANE D. WOBKEN, JANE D. WOBKEN Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this authorKERRY J. BERG, KERRY J. BERG Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this authorCATHERINE GATTO, CATHERINE GATTO Departments of Pediatrics University of Minnesota and Hennepin County Medical Center Minneapolis, MinnesotaSearch for more papers by this author First published: December 1988 https://doi.org/10.1111/j.1749-6632.1988.tb23947.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume547, Issue1Bombesin‐Like Peptides in Health and DiseaseDecember 1988Pages 532-533 RelatedInformation

Impaired beta-receptor function has been postulated as one factor contributing to airway hyperreactivity in asthmatic patients. Although numerous indirect studies have cast doubt on this theory, none of these previous investigations has been able to directly measure changes in beta-receptor number on intrapulmonary structures capable of affecting the physiologic changes seen in this disease state. To help clarify the intrapulmonary location of such changes, a model of allergic bronchoconstriction was prepared by sensitizing guinea pigs to ovalbumin intraperitoneally (ip) 2 wk prior to testing (Group S). A second group of animals was sensitized to ovalbumin, then 2 wk later partially desensitized (Group D) during a 4- to 6-wk period by repeated exposure to increasing doses of nebulized ovalbumin with epinephrine rescue. Control animals received ip administered and nebulized normal saline alone. Pulmonary function assessed by plethysmography revealed an increase in airway resistance to 294 +/- 42% (SE) of control in Group S (p less than 0.005) and a decrease in dynamic compliance to 76 +/- 8% of control in Group D and 39 +/- 10% of control in Group S (p less than 0.002) after exposure to nebulized ovalbumin. Using L-[3H] dihydroalprenolol ([3H] DHA), beta-receptors were autoradiographically localized and quantitated in lung sections from all 3 groups. Significant decreases (p less than 0.02) in 3H-DHA binding were noted in alveolar and conducting airway epithelium, and bronchiolar and vascular smooth muscle in ovalbumin-exposed animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitation using tissue homogenates has demonstrated a decrease in pulmonary β-receptors in experimental asthma. However, techniques using disrupted tissue have not permitted precise identification of the pulmonary structures where such decreases occur. Experimental asthma (A) was produced in guinea pigs by the sc injection of ovalbumin then daily exposure to ovalbumin aerosol for 4–5 weeks. Animals initially developed dyspnea during the aerosol exposures, but showed a tolerence to increasing ovalbumin concentrations over time. Using 3H-dihydroalprenolol, β-receptors were radioautographically localized and quantitated in lung sections of saline control (C) (n=6) and (A) (n=9) guinea pigs. Scatchard analysis showed a single class of binding sites with a Bmax of 368±32(C) and 258±15(A) fmole/mg protein (p<.005). Binding was of high affinity Kd=0.89±.09(C), 0.77±0.07(A) nM (N.S.). A 25–30% decrease in β-receptor number in alveolar, bronchiolar and bronchial epithelium (E) and bronchiolar smooth muscle (SM) (p<.001) appeared to be responsible for the 30% decrease in total (A) lung β-receptors. No decreases were noted in bronchial, arterial or venous SM. Despite the decrease in β-receptors no significant differences were noted in tidal volume, dynamic compliance and airway resistance between (C) and (A) animals in response to antigen challange as determined by body plethysmography immediately prior to sacrifice. These data suggest that decreases in β-receptor number can occur without changes in pulmonary function and decreases in E rather than SM β-receptors account for the majority of the observed change.

Studies using tissue homogenates have demonstrated an increase in pulmonary beta-receptors during development. However, techniques using disrupted tissue have not permitted the precise anatomic localization of pulmonary beta-receptors or identification of structures where increases occur. Using L-[3H]dihydroalprenolol, beta-receptors were radioautographically localized and quantitated in sections of newborn (NB) and adult (A) guinea pig lung. Scatchard analysis showed a single class of binding sites with a maximum binding capacity of 189 +/- 3 (NB) and 305 +/- 37 (A) fmol X mg-1 protein (P less than 0.02). Binding was of high affinity with the dissociation constant (Kd) = 1.46 +/- 0.2 (NB) and 1.26 +/- 0.3 (A) nM (NS). The majority of beta-receptors were localized in alveolar wall and airway epithelia (alveolar much greater than bronchiolar greater than bronchial) (P less than 0.0001). Airway and vascular smooth muscle had significantly fewer demonstrable beta-receptors. The increased number of beta-receptors in the adult appeared to be due primarily to a 2.0 +/- 0.12-fold increase in alveolar wall and airway epithelia as opposed to only a 1.3 +/- 0.18-fold increase in the already low number in airway and vascular smooth muscle (P less than 0.05). While apparent receptor density may not necessarily correlate with physiological response or importance, radioautographic localization of pulmonary beta-receptors may significantly enhance our understanding of their role in normal and pathologic states.