VIP-induced alterations in cAMP and inositol phosphates in the lower esophageal sphincter

Adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophospahte (cGMP), and inositol phosphate (IP) levels were measured in thin tissue samples from the circular smooth muscle of the cat lower esophageal sphincter (LES) at 37°C during vasoactive intestinal peptide (VIP)-induced relaxation. On exposure of in vitro LES circular muscle strips to 10^-6 M VIP at the same temperature, relaxation of spontaneous resting tone begins within 3-6 s, is half maximal at 30 s, and maximal at 1 min. VIP-induced changes in cAMP, cGMP, and IP metabolite levels were measured at 5 and 30 s after the addition of 10^-6 M VIP. At 5 s cAMP levels increased significantly with respect to time-matched unstimulated controls, whereas inositol 1,4,5-trisphosphate (1,4,5-IP₃) decreased and these changes remained constant at 30 s. cGMP levels were unchanged at either 5 or 30 s after exposure to 10^-6 M VIP. These data suggest that VIP-induced relaxation is temporally linked to decreased 1,4,5-IP₃ as well as increased cAMP levels.