Figure 1. Means by which VIP (or other cAMP-elevating agents) stimulates Cl^– secretion by airway gland serous cells.

(A) Low levels of VIP are insufficient to stimulate Cl^– secretion but do elevate cAMP sufficiently to open CFTR. Low levels of acetylcholine (ACh) (also subthreshold for secretion) raise [Ca²⁺]_i sufficiently to open basolateral K⁺ channels (G_K). Together, the two agents induce Cl^– secretion, as previously suggested by Choi et al. (10). (B) High levels of VIP elevate cAMP sufficiently to activate both Cl^– and K⁺ channels, as previously suggested by Choi et al. (10). (C) cAMP elevates [Ca²⁺]_i, which then activates basolateral K⁺ channels, as described by Lee and Foskett (9). (D) If the effects of cAMP on [Ca²⁺]_i are somehow enhanced then VIP can induce Cl^– secretion in CF cells by activating CaCC, as suggested by Lee and Foskett (9).