Open AccessSodium channel blockers and uridine triphosphate: effects on nasal potential difference in cystic fibrosis mice
Author(s) -
Ghosal S.,
Taylor C.J.,
Colledge W.H,
Ratcliff R,
Evans M.J
Publication year - 2000
Publication title -
european respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.021
H-Index - 241
eISSN - 1399-3003
pISSN - 0903-1936
DOI - 10.1034/j.1399-3003.2000.15a27.x
Subject(s) - chemistry , uridine triphosphate , endocrinology , purinergic receptor , medicine , uridine , chloride channel , cystic fibrosis transmembrane conductance regulator , cystic fibrosis , pharmacology , extracellular , biochemistry , nucleotide , biology , rna , gene
Sodium channel inhibitors block the enhanced Na + reabsorption in cystic fibrosis (CF). Extracellular nucleotides facilitate Cl ‐ secretion via Ca 2+ gated Cl ‐ channels. A combination of these effects may produce less viscid secretions in CF which are easier to expectorate. This study examined the effects of combining sodium channel blockers with uridine triphosphate (UTP) on nasal membrane potential difference (PD) in CF insertional null mutant mice ( cftr tmIHGU ), ΔF508 homozygous mice ( cftr tm1Cam ) and matched control animals. Median basal PD in the insertional CF mice and ΔF508 CF mice were ‐28 and ‐34 mV respectively. These values were significantly different to the control animals (‐20 mV). Amiloride and loperamide reduced the PD in cftr tmlHGU CF mice (ΔPD 13 mV & 15 mV respectively) suggesting Na + blockade. The subsequent addition of UTP in a chloride‐free vehicle increased the PD (ΔPD ‐8– ‐12.5 mV). ΔF508 mice showed significantly greater responses compared with CF insertional null mutant mice (p<0.05). The action of UTP was brief and not prolonged by the addition α‐β‐methylene‐adenosine 5′ diphosphate. Suramin, a competitive antagonist of P2 purinoceptors blocked the action of UTP. In conclusion, this study demonstrated dose dependant nasal membrane potential changes in differences mice with uridine triphosphate in the presence of sodium channel blockers suggestive of chloride secretion. More stable analogues of uridine triphosphate in combination with long acting sodium channel blockers such as loperamide may have therapeutic potential in cystic fibrosis.