Effect of sensory neuropeptides on mucus secretion from cultured goblet cells

Abstract

Background: Airway goblet cell secretion is under the control of capsaicin-sensitive sensory nerves. Administration of capsaicin or antidromic stimulation of nerves can stimulate goblet cell secretion and also induce plasma exudation and smooth muscle contraction via a release of neuropeptides from sensory nerve endings in the airway. This study was designed to explore whether the effect of capsaicin or neuropeptides on goblet cell secretion is direct or secondary to other airway responses.

Materials and methods: We examined the effects of sensory neuropeptides including substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), as well as capsaicin on cultured guinea pig tracheal goblet cells by measuring the rate of mucus discharge visually under a microscope and the release of 35SO4 radiolabeled mucin-like glycoconjugates.

Results: Goblet cells in culture spontaneously secreted intracellular granules at a mean rate of about 3 times/min. SP and NKA increased secretion in a dose-dependent manner. SP was more potent than NKA with maximum responses of 52% and 37% at 10(-8) M, respectively. Quantitative measurements of 35SO4 radiolabeled mucin-like glycoprotein (MLGP) secreted by goblet cells also revealed an increase (109.2%) in mucin secretion caused by SP (10(-8) M) compared with the vehicle control. Neither capsaicin nor NKB caused any significant change in the goblet cell secretory rate. The effects of SP on the secretory rate or release of radiolabeled mucin were not potentiated by an enkephalinase inhibitor, thiorphan (10(-5) M).

Conclusion: Sensory neuropeptides SP and NKA directly stimulate goblet cell secretion, probably through the tachykinin receptor of the NK-1 subtype as suggested by a greater potency of SP. There was no direct effect of capsaicin on goblet cell secretion.