Clomipramine induces the opening of Na+ channels in the frog skin epithelium.
This paper studies the effect of clomipramine on the electrical parameters of the frog skin epithelium. We have found that clomipramine induces: 1) an increase in short circuit current that is equivalent to an increase in net Na+ flux, 2) an increase in total transepithelial conductance, 3) a depolarisation of the apical barrier, and 4) a decrease in the fractional resistance of the apical membrane. These results suggest that clomipramine promotes an increase in the sodium permeability of the apical barrier by increasing either the concentration of amiloride-sensitive Na+ channels or by increasing their individual conductance. Using kinetic models, values for the affinity constants for clomipramine and amiloride were estimated (K(Clo)=(18.l +/- l.04) x l0(-6) M; K(Amil) = 56 x 10(-8) M). Identical studies were performed for eel intestinal epithelium and no significant changes on the short circuit current were observed.
Alves
Paula E
PE
Department of Chemistry, Center of Fine Chemistry and Biotechnology (CQFB), Faculty of Sciences and Technology, New University of Lisbon, Quinta da Torre, Caparica, Portugal.
Graça
Inês C
IC
Moura
Teresa E
TE
D000465:Algorithms; D000584:Amiloride / Q000494:pharmacology; D000811:Anguilla; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D010121:Oxytocin / Q000494:pharmacology; D011898:Ranidae; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D015222:Sodium Channels; D010121:Oxytocin; D000584:Amiloride; D012964:Sodium; D002997:Clomipramine