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Differential effects of UTP and ATP on ion transport in porcine tracheal epithelium
Author(s) -
Inglis S K,
Olver R E,
Wilson S M
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703324
Subject(s) - staurosporine , thapsigargin , transepithelial potential difference , p2y receptor , ion transporter , uridine triphosphate , amiloride , medicine , endocrinology , chemistry , protein kinase c , receptor , biology , purinergic receptor , biochemistry , kinase , extracellular , nucleotide , sodium , organic chemistry , membrane , gene
Isolated segments of porcine tracheal epithelium were mounted in Ussing chambers, current required to maintain transepithelial potential difference at 0 mV (short circuit current, I SC ) was monitored and effects of nucleotides upon I SC were studied. Mucosal UTP (100 μ M ) evoked a transient rise in I SC that was followed by a sustained fall below basal I SC maintained for 30 min. Mucosal ATP (100 μ M ) also stimulated a transient rise in I SC but in contrast to UTP did not inhibit basal I SC . Submucosal UTP and ATP both transiently increased I SC . UTP‐prestimulated epithelia were refractory to ATP but prestimulation with ATP did not abolish the response to UTP. The epithelia thus appear to express two populations of apical receptors allowing nucleotides to modulate I SC . The UTP‐induced rise was reduced by pretreatment with either bumetanide (100 μ M ), diphenylamin‐2‐carboxylic acid (DPC, 1 m M ), or Cl − and HCO 3 − ‐free solution whilst the fall was abolished by amiloride pretreatment. Thapsigargin (0.3 μ M ) abolished the UTP‐induced increase in I SC but not the subsequent decrease. Staurosporine (0.1 μ M ) inhibited basal I SC and blocked UTP‐induced inhibition of I SC . Inhibitors of either protein kinase C (PKC) (D‐erythro sphingosine) or PKA (H89) had no effect. This study suggests that UTP stimulates Cl − secretion and inhibits basal Na + absorption. ATP has a similar stimulatory effect, which may be mediated by activation of P2Y 2 receptors and an increase in [Ca 2+ ] in , but no inhibitory effect, which is likely mediated by activation of a pyrimidine receptor and possible inhibition of a protein kinase other than PKC or PKA.British Journal of Pharmacology (2000) 130 , 367–374; doi: 10.1038/sj.bjp.0703324