Carbamylcholine‐ and 5‐hydroxytryptamine‐induced contraction in rat isolated airways: inhibition by calcitonin gene‐related peptide

Cadieux, Alain; Lanoue, C.; Sirois, Pierré; Barabé, J.

doi:10.1111/j.1476-5381.1990.tb12112.x

Cited by 21 publications

(15 citation statements)

References 31 publications

(42 reference statements)

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“…In other animal species, CGRP has been shown to have no contractile effect on the airway smooth muscle in the rabbit (26), pig (27,28), rat (10,20), and mouse (29) in vitro and in the sheep in vivo (30). Finally, CGRP has been noted to cause relaxations in pig trachea (27) and bronchi (28) precontracted with carbamylcholine and histamine, respectively, and in mouse airways precontracted with carbachol (29).…”

Section: Discussionmentioning

confidence: 92%

“…The inhibitory effect of CGRP on SP-induced contractions was investigated essentially as described previously (10). Each tissue preparation was first primed with a concentration of carbamylcholine (10 Ϫ 6 M) to evaluate its responsiveness.…”

Section: In Vitro Measurements Of Airway Responsesmentioning

confidence: 99%

“…We have previously shown that CGRP exerts a potent and concentration-related inhibition on bronchospasms induced by carbamylcholine and 5-HT in rat isolated airways. Interestingly, this bronchoprotective effect of CGRP was found to be more powerfully expressed in distal than in proximal airways, suggesting that CGRP might be of functional importance mainly in the periphery of the tracheobronchial tree (10). In view of the importance given to the sensory neuropeptides in the pathogenesis of asthma and because CGRP is also associated with neurogenic reflexes in the lung, we found it worthwhile to further investigate this interesting property of CGRP to downregulate the airway responsiveness.…”

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confidence: 95%

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

Cadieux

Monast

Pomerleau

et al. 1999

Am J Respir Crit Care Med

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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.

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Section: Discussionmentioning

confidence: 92%

Section: In Vitro Measurements Of Airway Responsesmentioning

confidence: 99%

mentioning

confidence: 95%

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

Cadieux

Monast

Pomerleau

et al. 1999

Am J Respir Crit Care Med

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“…(Tschirhart et al, 1990) and in the human bronchus (Palmer et al, 1987) in vitro. On the other hand, CGRP is shown to have no effect on the airway smooth muscle in the guinea-pig (Bhogal et al, 1994) and pig trachea (Kannan & Johnson, 1991) in vitro and in the sheep in vivo (Parsons et al, 1992), and to cause inhibition of the carbachol-and 5-hydroxytryptamine-induced contraction of rat isolated airways (Cadieux et al, 1990). Furthermore, CGRP is reported to cause relaxations in guinea-pig trachea precontracted with KCl and PGF2a (Bhogal et al, 1994) and in pig trachea (Kannan & Johnson, 1992) and mouse bronchus (Manzini, 1992) precontracted with carbachol.…”

Section: Cholinergic Contraction In Tracheal Ringsmentioning

confidence: 99%

Effects of adrenomedullin and calcitonin gene‐related peptide on airway and pulmonary vascular smooth muscle in guinea‐pigs

Pinto

Sekizawa

Yamaya

et al. 1996

British J Pharmacology

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1 The airway and pulmonary vascular effects of adrenomedullin were studied in the guinea-pig isolated trachea, main bronchi and pulmonary artery in vitro and compared to the effects of calcitonin generelated peptide (CGRP).2 In tracheal rings, CGRP (1 nM to 1 gM) potentiated the cholinergic contractions induced by electrical field stimulation (EFS) at 5 Hz in a concentration-dependent manner. At a concentration of 1 gM, CGRP slightly decreased the responses to log EFS frequency, producing 50% of the maximum contraction from a control value of 0.77+0.10 Hz to 0.54+0.05 Hz without a significant effect on the concentration-response curves to acetylcholine (ACh). In contrast, adrenomedullin (1 nM to 1 gM) did not alter either EFS-induced cholinergic or ACh-induced contractions. 3 In bronchial strips, CGRP (1 nm to 1 pM) slightly reduced both the non-adrenergic non-cholinergic (NANC) contraction induced by EFS at 10 Hz and the substance P (1 gM)-induced contraction in a concentration-dependent manner, whereas adrenomedullin (1 nM to 1 pM) was without effect.4 Neither CGRP (1 gM) nor adrenomedullin (1 gM) altered NANC relaxation induced by EFS at 5 Hz in tracheal rings precontracted with histamine (10 gM). Adrenomedullin (1 nm to 1 gM) and CGRP (1 nM to 1 pM) induced a concentration-dependent relaxation of the histamine (10 pM)-and prostaglandin F2a (10 gM)-precontracted pulmonary arterial rings with intact endothelium with a similar potency.6 Neither removal of the endothelium nor NG-nitro-L-arginine methyl ester (100 pM) altered the vasorelaxant effects of adrenomedullin (1 nM to 1 pM) and CGRP (1 nM to 1 gM). 7 The putative CGRP receptor antagonist, CGRP8-37 (1 MM to 10 gM) concentration-dependently attenuated the CGRP (3 nM to 30 nM)-induced vasorelaxant actions, whereas it had no effect on the relaxation of vessel rings induced by adrenomedullin (3 nM to 30 nM). 8 These results suggest that adrenomedullin is a potent vasodilator of the pulmonary artery without any bronchomotor effect in the guinea-pig lung, and that the vasorelaxant actions of adrenomedullin are not mediated via the activation of CGRP1 receptors.

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“…CGRP modulates contraction induced by 5-HT or carbachol in the airway [7] and the actions of vasodilators [3]. It has been reported that in airway epithelia CGRP modulates ciliary beat frequency and mucus secretion [33] and causes proliferation of epithelial cells [37].…”

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confidence: 98%

Cl - secretion induced by 5-hydroxytryptamine and calcitonin gene-related peptide in rat tracheal epithelia

Jung

Kim

et al. 1997

Pfl�gers Archiv European Journal of Physiology

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The effects of 5-hydroxytryptamine (5-HT) and calcitonin gene-related peptide (CGRP), which are colocalized in nerve terminals in the airway, on Cl- secretion in rat tracheal epithelia were tested. Short-circuit current (Isc) was measured after rat tracheal epithelial monolayers were cultured on porous filters. In rat tracheal monolayers 5-HT and CGRP increased Isc upon addition to the serosal compartment, in a dose-dependent manner with EC50 values at 5 micromol/l and 5 nmol/l, respectively. The responses were dependent on the presence of Cl- in the bathing solution and were inhibited by 100 micromol/l bumetanide. When 5-HT or CGRP was added after the administration of forskolin, the responses were not observed. 5-HT and CGRP increased the intracellular cAMP concentration. Low-Ca2+ buffer (0.1 mmol/l) and pretreatment with BAPTA/AM (10 micromol/l), thapsigargin (1 micromol/l) or indomethacin (10 micromol/l) did not affect the responses to 5-HT and CGRP. The 5-HT-induced response was not inhibited by 5-HT2 and/or 5-HT4 antagonists. These results indicate that in the rat tracheal epithelia 5-HT and CGRP increase Cl- secretion by an increase in intracellular cAMP concentration via direct activation of basolateral receptors, and that the response to 5-HT is not mediated via 5-HT4 receptors.

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Carbamylcholine‐ and 5‐hydroxytryptamine‐induced contraction in rat isolated airways: inhibition by calcitonin gene‐related peptide

Cited by 21 publications

References 31 publications

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

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

Effects of adrenomedullin and calcitonin gene‐related peptide on airway and pulmonary vascular smooth muscle in guinea‐pigs

Cl - secretion induced by 5-hydroxytryptamine and calcitonin gene-related peptide in rat tracheal epithelia

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