P₂ purinoceptor regulation of mucin release by airway goblet cells in primary culture

Abstract

1 The effects of adenine analogues on mucin release by airway goblet cells have been examined in a hamster primary tracheal epithelial cell culture. 2 Adenosine, a P1 receptor agonist, had no effect on mucin release even at 2 mm, while ATP, a P2 receptor agonist, stimulated mucin release in a dose-dependent fashion with an apparent EC50 of 20,pM.The relative potency order among adenine nucleotides was ATP > ADP > AMP = adenosine.3 ATP, S, a non-hydrolyzable analogue of ATP, was equipotent with ATP in stimulating mucin release.The potency order among some ATP analogues was ATP > 2-methylthio ATP > a,4-methylene ATP > fy-methylene ATP. Reactive blue 2, a putative P2y-purinoceptor antagonist, did not block the ATP-induced mucin release. 4 The present results indicate that mucin release by airway goblet cells is stimulated by extracellular ATP via P2 receptor-mediated mechanism. We suggest that this mechanism may be important in the physiological regulation of airway goblet cell mucin release in vivo.

Defective ATP‐dependent mucin secretion by cystic fibrosis pancreatic epithelial cells

“…ATP, reported to be a potent secretagogue of electrolyte, has been consequently proposed for use as a therapeutic agent for cystic fibrosis in order to bypass the defective function of CFTR, and to restore chloride secretion in CF patients [5]. Recent reports demonstrate that extracellular ATP is also a very potent secretagogue of mucin secretion in goblet cells from the respiratory tract [6], via a P2-receptor-mediated mechanism [7,8], and of SLPI (secretory leucoprotease inhibitor) in human tracheal gland cells [9].…”

Localization of Nucleoside Triphosphate Diphosphohydrolase-1 (NTPDase1) and NTPDase2 in Pancreas and Salivary Gland

“…Molecular cloning of nucleotide receptors (P2 receptors) has allowed better physiological and pharmacological characterizations of these responses. P2 receptors are expressed in the cells of all organ systems in mammals (Abbracchio and Burnstock 1998;Fischer et al 1999), including the digestive system, where they regulate electrolyte secretion, glandular secretion (Rice and Singleton 1986;Kim and Lee 1991), smooth muscle contraction (Burnstock 1990;Fedan and Frazer 1992), and blood flow (Munoz et al 1999).…”

The lactoperoxidase system links anion transport to host defense in cystic fibrosis

“…Normal human airway epithelia also actively produce H 2 O 2 at the apical surface using Duox and release it into the apical surface liquid [18]. This airway H 2 O 2 production is increased through stimulation of purinergic receptors [18] that also act to increase mucus secretion [19,20] and ciliary beating [21][22][23] LPO system is present in the airway lumen and can be regulated in concert with other facets of the airway host defense. Since the LPO system is effective against staphylococci [24], E. coli and pseudomonads [24][25][26] and since SCN À is a requisite substrate for LPO, defects in SCN À transport and resulting loss of LPO activity could contribute, at least partially, to the chronic respiratory infections seen in CF patients.…”