Dictamine Stimulates Cystic Fibrosis Transmembrane Conductance Regulator CL− Transport

Dictamine is a furoquinoline alkaloid isolated from Dictamus dasycarpus Turcz. In the present study, we found that dictamine is able to stimulate the chloride transport activity of wild-type and ΔF508 mutant CFTR. The activity is cAMP-dependent and can be completely reversed by specific CFTR inhibitor CFTRinh-172. In addition, dictamine can further increase the chloride transport activity when CFTR is maximally activated by the combination of cAMP stimulators forskolin (FSK) and IBMX, suggesting direct interaction of dictamine with CFTR. Dictamine may be useful for probing CFTR channel gating mechanisms and used as a lead compound to develop the pharmacological therapy of CFTR-related diseases such as idiopathic chronic pancreatitis and keratoconjunctivitis sicca and cystic fibrosis.