Vasotocin and vasopressin stimulation of the chloride secretion in the human bronchial epithelial cell line, 16HBE14o-.
1. Effects of neuropeptides of the vasopressin family on Cl(-) secretion have not yet been reported in lung. Using the 16HBE14o- bronchial epithelial cell line, we investigated their action on Cl(-) secretion. 2. In symmetrical Cl(-) solutions, basolateral application of arginine vasotocin (AVT), oxytocin or isotocin induced a transient I(sc) stimulation (I(peak)), whereas arginine vasopressin (AVP) did not. The effects of different Cl(-) channel blockers and of a protein kinase C (PKC) inhibitor suggest that CFTR is involved in I(peak). The calcium-activated K(+) channel (SK4) and the Cl(-)/HCO(-)(3) exchanger favor the driving force for AVT-mediated Cl(-) secretion. The antagonists of V1a (SR49059)- and V1b (SSR149415)-receptors blocked I(peak), while SR121463B, a V2 receptor antagonist, did not. These results point to the stimulation of a V1-like receptor mediating I(peak) and presenting an efficacy order, AVT>oxytocin>isotocin>>AVP. 3. When a serosal to mucosal Cl(-) gradient was applied, AVT and AVP both stimulated I(sc) according to a biphasic profile, I(peak) being followed by a plateau phase (I(plateau)). The pharmacology of I(plateau) suggests that CFTR channels are involved and that Na(+)/K(+)/2Cl(-) is the only transporter associated with I(plateau). dDAVP, a V2 receptor agonist-induced I(plateau) with the same potency as AVP, suggesting the involvement of V2 receptors in the AVP-induced I(plateau). V2 receptors are present on both opposite membranes, while V1-like receptors are mainly expressed on the basolateral membranes. RT-PCR experiments show the expression of V1a, V1b, V2 and vasopressin-activated calcium-mobilizing (VACM) receptors mRNAs.
Bernard
Karen
K
Laboratoire de Physiologie des Membranes Cellulaires, Université de Nice-Sophia Antipolis, FRE 2721/CNRS (Batiment Jean Maetz), 06230 Villefranche-sur-Mer, France.
Bogliolo
Stéphanie
S
Ehrenfeld
Jordi
J
D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017483:Receptors, Vasopressin / Q000819:agonists / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology*; D014668:Vasotocin / Q000494:pharmacology*
D018118:Chloride Channels; D017483:Receptors, Vasopressin; D014667:Vasopressins; D014668:Vasotocin