Capsaicin and sensory neuropeptide stimulation of goblet cell secretion in guinea‐pig trachea.

Abstract

SUMMARY1. We studied the effect of capsaicin and sensory neuropeptides on tracheal goblet cell secretion in anaesthetized guinea-pigs using a semi-quantitative morphometric technique whereby the magnitude of discharge of stained intracellular mucus, expressed as a mucus score (MS), was related inversely to discharge.2. Capsaicin (I.v.) induced goblet cell secretion: a decrease of 50% in MS below control (indicative of increased secretion) was maximal at 3-3 x 10-1 mol/kg.3. Capsaicin-induced secretion was unaffected either by prior vagus nerve section or by pre-treatment with atropine, propranolol and phentolamine which suggests that local axon reflexes with release of sensory neuropeptides are involved in the response.4. Intravenous substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and calcitonin gene-related peptide (CGRP) produced dose-related increases in goblet cell secretion, with SP the most potent. Doses (mol/kg) causing a 50% decrease in MS from control were 3-5 x 0-12 for SP; 72 x 10"1 for NKA; 1-6 x 10-9 for NKB; and 1-2 x 10-8 for CGRP. The maximal increase in goblet cell secretion was 75% of control and occurred with SP at 10-10 mol/kg. 5. SP-induced mucus discharge was not inhibited by atropine or the histamine receptor antagonists mepyramine or cimetadine. 6. We conclude that in guinea-pig trachea, goblet cell secretion is under the control of capsaicin-sensitive sensory nerves and release of neuropeptides from these nerves may induce mucus discharge via tachykinin receptors of the NK-1 subtype (indicated by an order of potency of SP > NKA > NKB).

Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction

“…32 Degranulation of goblet cells is triggered by the activation of these nerve fibers. 33 In the guinea pig model of hyperpneainduced bronchoconstriction, a NK2 receptor antagonist inhibited bronchoconstriction without altering the LT levels, whereas either a cysLTR 1 antagonist or a 5-LO inhibitor significantly reduced bronchoconstriction and the release of SP. 34 Similar results were identified in the dog model of hyperpnea-induced bronchoconstriction using a combination of NK1 and NK2 antagonists.…”

Toxic Rhinitis-Induced Changes of Human Nasal Mucosa Innervation

“…As shown here and previously, SP-immunoreactive nerve fibers are located around glands and blood vessels, between smooth muscle myocytes and subepithelially. Its biological effects in upper airways consist of plasma extravasation, vasodilatation, and increased glandular secretion and mucociliary clearance (2,21,31).…”

Bronchial Hyperreactivity in the Peripheral Airways.

“…Shimura et al (1990) have investigated the mechanism of glucocorticoid inhibitory action on mucus glycoprotein secretion from feline trachea and concluded that the inhibitory effect of glucocorticoid is due to a reduction in the release from secretory cells with no alteration in synthesis and/or uptake of mucus precursor. Kuo et al (1990) suggested that goblet cell secretion is under the control of capsaicin-sensitive sensory nerves and the release of neuropeptides from these nerves may induce mucus discharge via tachykinin receptors of the neurokinin-1 subtype. However, mucus secretion from goblet cells in the peripheral airway has not been studied yet.…”