Bronchoprotector Properties of Calcitonin Gene–related Peptide in Guinea Pig and Human Airways

Abstract

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.

Calcitonin gene‐related peptide mediates acid‐induced lung injury in mice

“…αCGRP is present in the central and peripheral nervous systems, 7 while βCGRP is expressed in specific neuronal sites 8 . In the respiratory system, CGRP is synthesized by sensory C‐fibres throughout the respiratory tree 9,10 and is reported to be involved in the regulation of airway physiology 11,12 . CGRP is also found in neuroepithelial cells of the lung and coexists with tachykinins in many airway sensory nerves, 13 while CGRP receptors are found in lung vessels 14 .…”

“…8 In the respiratory system, CGRP is synthesized by sensory C-fibres throughout the respiratory tree 9,10 and is reported to be involved in the regulation of airway physiology. 11,12 CGRP is also found in neuroepithelial cells of the lung and coexists with tachykinins in many airway sensory nerves, 13 while CGRP receptors are found in lung vessels. 14 It has been shown that CGRP, a potent vasodilator, 15 modulates hypoxic pulmonary vasoconstriction.…”

Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide

“…Recent studies using genetically engineered mice have shown that CGRP-knockout mice exhibit increased blood pressure (10). CGRP is synthesized by sensory C-fibers throughout the respiratory tree and potently constricts airway smooth muscle (11). The tissues contained considerably more CGRP than another neuropeptide, substance P (12, 13).…”

Roles of calcitonin gene-related peptide in ehancement of angiogenesis

“…Recent studies using genetically engineered mice have shown that CGRP-knockout mice exhibit increased blood pressure 9) . CGRP is synthesized by sensory C-fibers throughout the respiratory tree, and potently constricts airway smooth muscle 10) . The tissues contained considerably more CGRP than another neuropeptide, substance P, CGRP 11,12) .…”