S-carbocysteine-lysine salt monohydrate and cAMP cause non-additive activation of the cystic fibrosis transmembrane regulator channel in human respiratory epithelium.
S-Carbocysteine-lysine salt monohydrate (S-CMC-Lys) has been shown to open a Cl- channel in the trachea, thus aiding fluid secretion. The aim of this study was to characterize the channel and the action mechanism on a culture line of human respiratory epithelial cells. The patch-clamp technique (in cell-attached or inside-out configuration) and conventional micro-electrodes were used. The activity and density of a cAMP-dependent Cl- channel, identical to the cystic fibrosis transmembrane regulator (CFTR) channel, proved to be maximally stimulated by 100 microM S-CMC-Lys present in the cAMP-free cell incubation medium for 240-290 min (cell-attached configuration). Subsequent addition of cAMP to the medium did not determine any further activation. S-CMC-Lys acted mostly indirectly as, when placed in direct contact with a membrane patch, activation of the CFTR channel was nil (cytoplasmic side) or limited (external side).
Meyer
G
G
Dipartimento di Fisiologia e Biochimica Generali, Università degli Studi di Milano, Italy.
Doppierio
S
S
Daffonchio
L
L
Cremaschi
D
D
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D002233:Carbocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects* / Q000378:metabolism*; D005347:Fibroblasts; D006801:Humans; D008239:Lysine; D018408:Patch-Clamp Techniques; D012137:Respiratory System
C505032:CFTR protein, human; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C034932:carbocysteine-lysine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002233:Carbocysteine; D008239:Lysine