Vasotocin and vasopressin stimulation of the chloride secretion in the human bronchial epithelial cell line 16HBE14o-

摘要

class="enumerated" style="list-style-type:decimal">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.In symmetrical Cl⁻ solutions, basolateral application of arginine vasotocin (AVT), oxytocin or isotocin induced a transient Isc stimulation (Ipeak), 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 Ipeak. 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 Ipeak, while SR121463B, a V2 receptor antagonist, did not. These results point to the stimulation of a V1-like receptor mediating Ipeak and presenting an efficacy order, AVT>oxytocin>isotocin≫AVP.When a serosal to mucosal Cl⁻ gradient was applied, AVT and AVP both stimulated Isc according to a biphasic profile, Ipeak being followed by a plateau phase (Iplateau). The pharmacology of Iplateau suggests that CFTR channels are involved and that Na⁺/K⁺/2Cl⁻ is the only transporter associated with Iplateau. dDAVP, a V2 receptor agonist-induced Iplateau with the same potency as AVP, suggesting the involvement of V2 receptors in the AVP-induced Iplateau. 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.