Calcitonin gene‐related peptide is localised to human airway nerves and potently constricts human airway smooth muscle

Palmer, Jamie; Cuss, Francis M.; Mulderry, P.K.; Ghatei, M. A.; Springall, David R.; Cadieux, Alain; Bloom, Stephen R.; Polak, Julia M.; Barnes, Peter J.

doi:10.1111/j.1476-5381.1987.tb08987.x

Cited by 129 publications

(40 citation statements)

References 22 publications

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“…In agreement with Malm & Petersson (1985) we have not observed any effect of topical SP at a dose capable of inducing facial flushing. Nerve fibres, containing CGRP, have recently been shown in the human airways (Palmer et al, 1987). Functional evidence has been presented indicating that CGRP may be responsible for many acute responses to capsaicin which cannot be ascribed to SP (Franco-Cereceda & Lundberg, 1985;Hua & Lundberg, 1986).…”

Section: Discussionmentioning

confidence: 99%

Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man

Geppetti

Fusco

Marabini

et al. 1988

British J Pharmacology

123

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Section: Discussionmentioning

confidence: 99%

Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man

Geppetti

Fusco

Marabini

et al. 1988

British J Pharmacology

123

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“…SP and two newer members of the tachykinin family, neurokinin A (NKA) and neurokinin B (NKB) have been shown to increase vascular permeability in guinea-pig trachea (Lundberg et al, 1985) although, of the two neurokinins, only NKA has been localized to capsaisin-sensitive nerves in the guinea-pig (Hua et al, 1985a). Recently, calcitonin gene-related peptide (CGRP) has been localized to airway nerves in rat (Cadieux et al, 1986;Lauweryns & Van Rast, 1987) and man (Palmer et al, 1987 Lundberg et at., 1985;Gulbenkian et al, 1986). CGRP exhibits potent vasodilator activity but, unlike the tachykinins, does not increase vascular permeability in guinea-pig trachea (Lundberg et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Effects and interactions of sensory neuropeptides on airway microvascular leakage in guinea‐pigs

Rogers

Belvisi

Aursudkij

et al. 1988

British J Pharmacology

Self Cite

123

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1 We have studied the effect of the sensory neuropeptides substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) on microvascular permeability in guinea-pig airways in vivo and investigated whether CGRP would potentiate the effect of SP. We used the extravasation of intravenously-injected Evans blue dye as an index of permeability. 2 The tachykinins SP, NKA and NKB (0.025-5.Onmol kg-, i.v.) significantly (P <0.05) increased extravasation of dye in a dose-related manner and with a similar pattern of distribution; they were most potent in the trachea and main bronchi, less potent in the larynx and intrapulmonary airways, and had little significant effect in the bladder.3 SP was significantly more potent in causing extravasation of dye than NKA or NKB with ED50 values (nmol kg-1) in the range 0.04-0.1, depending on the airway level, compared with values in the range 0.3-0.7 for the neurokinins. 4 CGRP (0.0025-2.5 nmol kg-1, i.v.) had no significant effect on microvascular permeability and did not potentiate SP-induced extravasation of dye. 5 Each neuropeptide decreased mean arterial blood pressure, indicating vasodilatation, in a doserelated manner. Co-injection of CGRP and SP produced additive decreases in arterial pressure. 6 We conclude that, in guinea-pig airways, tachykinins increase microvascular permeability via tachykinin receptors of the NK-1 sub-type (indicated by an order of potency of SP > NKA = NKB) on endothelial cells. The response appears to be related to mechanisms in addition to vasodilatation. The relevance of the responses to the tachykinins in asthma is discussed. IntroductionElectrical stimulation of the cervical vagus nerves in rat and guinea-pig induces a number of physiological responses including vasodilatation and increased permeability of the microvasculature of the trachea to macromolecules (Lundberg & Saria, 1982;Lundberg et al., 1983). Both responses are preserved in the presence of atropine, hexamethonium or antihistaminic drugs, but are absent in animals pretreated with capsaicin. Capsaicin is the major pungent principle of hot peppers of the plant genus Capsicum and has been shown to deplete primary afferent C-fibres of stored neuropeptides (Buck & Burks, 1986). Capsaicin itself causes a depolarization of afferent Cfibres which induces local effects including vasodilatation and plasma extravasation in guinea-' Author for correspondence.pigs (Lundberg et al., 1984a). The physiological responses may, therefore, be due to release of neuropeptides localized to capsaicin-sensitive nerves. For example, the tachykinin substance P (SP) has been localized to sensory nerves in the airways of several species, including man (Lundberg et al., 1984b). SP and two newer members of the tachykinin family, neurokinin A (NKA) and neurokinin B (NKB) have been shown to increase vascular permeability in guinea-pig trachea (Lundberg et al., 1985) although, of the two neurokinins, only NKA has been localized to capsaisin-sensitive nerves in the guinea-pig (Hua...

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“…The effects of bradykinin may be due to release of sensory neuropeptides such as calcitonin gene-related peptide and the tachykinins substance P and neurokinin A, which have been localised to airways in animals and man (Lundberg et al, 1984;Polak & Bloom, 1982;Martling et al, 1987;Ueda et al, 1984) and have been shown to have potent bronchoconstrictor actions in human airways (Martling et al, 1987;Barnes, 1987;Joos et al, 1987;Palmer et al, 1987;Evans et al, 1988). Thus bradykinin may release sensory neuropeptides as part of an axon reflex (Barnes, 1986), and it is possible that sodium cromoglycate and nedocromil sodium interfere with this response.…”

Section: Discussionmentioning

confidence: 99%

Bradykinin‐induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate.

Dixon

Barnes

1989

Brit J Clinical Pharma

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1 The effects of inhaled nedocromil sodium and sodium cromoglycate on bradykinininduced bronchoconstriction have been studied in a double-blind, placebo controlled study, in eight mild asthmatic subjects. 2 The subjects attended on four occasions. Fifteen minutes after drug pre-treatment a bradykinin challenge was performed. Increasing concentrations were inhaled until a greater than 40% fall in expiratory flow at 30% of vital capacity from a partial flow volume manoeuvre (Vp30) was demonstrated.3 Inhaled bradykinin (0.06-8.0 mg ml-1) caused dose-related bronchoconstriction with the geometric mean cumulative dose causing a 40% fall in Vp3o (PD40) of 0.035 (95% CI: 0.02-0.07) ,umol, after placebo inhalation, which was similar to that measured before the trial (0.04: 0.02-0.09 ,umol). 4 Both nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) gave significant protection (P < 0.05) against bradykinin-induced bronchoconstriction (PD40 0.37: 0.19-0.72 p,mol after nedocromil sodium and 0.22: 0.11-0.49 after sodium cromoglycate). 5 Since bradykinin-induced bronchoconstriction is probably neurally mediated we conclude that both nedocromil sodium and sodium cromoglycate have an action on neural pathways which may be useful in the control of asthma symptoms.

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Calcitonin gene‐related peptide is localised to human airway nerves and potently constricts human airway smooth muscle

Cited by 129 publications

References 22 publications

Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man

Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man

Effects and interactions of sensory neuropeptides on airway microvascular leakage in guinea‐pigs

Bradykinin‐induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate.

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