Effect of extracellular ATP and UTP on fluid transport by human nasal epithelial cells in culture.

Abstract

We have investigated the effect of both adenosine triphosphate (ATP) and uridine triphosphate (UTP) on the fluid transport, transepithelial electric potential difference (PD), and unidirectional chloride flux when applied apically to cultured human surface respiratory epithelial (HSRE) cells in a double-compartment chamber. The effects of ATP and UTP (both 100 microM) were examined in cells either untreated or pretreated with 100 microM amiloride in lactated Ringer's solution. ATP or UTP was added to the apical solution in a 100 microliters final volume. After a 2-h incubation period, the change in fluid transport was measured by weighing the apical fluid. Compared with control, amiloride blocked the fluid absorption by HSRE cells. The addition of ATP or UTP, either alone or after pretreatment with amiloride, induced a similar and significant increase in the apical fluid and chloride flux (P < 0.001 and P < 0.005, respectively). The changes in both fluid transport and chloride flux were accompanied by changes in PD. A blocker for chloride transport, 4,4'-diisothiocyano-2,2'-stilbene disulfonate, at 500 microM significantly blocked the ATP-stimulated fluid transport (P < 0.05) and chloride flux (P < 0.01). These results support the hypothesis that extracellular ATP and UTP increase the fluid transport by respiratory epithelial cells and may be useful in the hydration of mucus and respiratory mucosa.

Purinergic Signaling in the Airways

“…Extracellular ATP increases fluid transport by human nasal epithelial cells in culture (Benali et al, 1994). Evidence was presented to suggest that ATP acts as a cotransmitter with NA in sympathetic nervous control of blood vessels of the nasal mucosa of cats and dogs (Lacroix et al, 1994).…”

Pharmacology of INS37217 [P1-(Uridine 5′)-P4- (2′-deoxycytidine 5′)tetraphosphate, Tetrasodium Salt], a Next-Generation P2Y2 Receptor Agonist for the Treatment of Cystic Fibrosis

“…The P2Y 2 receptor is abundant on the luminal surface of polarized epithelial cells, especially those lining mucosal surfaces exposed to the external environment. The pharmacology of the P2Y 2 receptor has been established, and the effects of P2Y 2 agonists on epithelial cell functions are numerous, including stimulation of serosal to mucosal chloride and fluid transport (Knowles et al, 1991;Benali et al, 1994;Tarran et al, 2000), enhancement of mucin secretion from goblet cells (Lethem et al, 1993;Kim et al, 1996), increase in cilia beat frequency (Morse et al, 2001), and promotion of surfactant release from type II alveolar cells (Gobran et al, 1994). Additionally, tracheal mucus velocity (TMV), a measure of mucociliary clearance in a single large airway, has revealed the mucokinetic effects of nucleotides and various other agents in the lung in vivo (Sabater et al, 1996).…”

Nucleotide-induced mucin release from primary hamster tracheal surface epithelial cells involves the P2u purinoceptor

“…Recently, LETHEM et al. [4] demonstrated that uridine triphosphate (UTP) is almost equipotent with adenosine triphosphate (ATP) in its ability to stimulate mucin release from human airway epithelial explants [4], suggesting the presence of a receptor type specific both for ATP and UTP in airway epithelial cells, which may regulate the mucin release.The presence of this type of purinoceptor has been identified in a number of systems [6,7], including airway epithelial cells, which involve the regulation of ion transport [8,9], and have recently been classified as the …”

“…The presence of this type of purinoceptor has been identified in a number of systems [6,7], including airway epithelial cells, which involve the regulation of ion transport [8,9], and have recently been classified as the…”