Increase in participation of vasoactive intestinal peptide in relaxation of the distal colon of Wistar rats with age

1 Changes in participation of vasoactive intestinal peptide (VIP) in nonadr energic noncholinergic (NANC) relaxation of longitudinal muscle of the dist al colon with age were studied in 2- to 50-week-old Wistar rats in vitro. 2 The extent of the VIP-mediated component of the relaxation induced by ele ctrical field stimulation (EFS) was determined by the effect of VIP10-28 a VIP receptor antagonist. In 2-week-old rats, the extent of the VIP-mediated component of the relaxation was scarce, about 10%, whereas the component g radually increase with age and reached the maximum extent 66% at 50-week-ol d. 3 Since our previous results suggest that VIP induces NANC relaxation via a ctivation of charybdotoxin (ChTx, a blocker of large conductance Ca2+-activ ated K+ channel)-sensitive K+ channels with concomitant slow hyperpolarizat ion in the muscle cells, we next studied whether ChTx-sensitive component a nd slow hyperpolarization changes with age. Extent of ChTx-sensitive compon ent of the relaxation increased with age, showing a very similar pattern to VIP-mediated one. 4 EFS induced monophasic inhibitory junction potentials (i.j.ps) in longitu dinal muscle cells of the distal colon of 2- and 4-week-old. EFS also induc ed biphasic i.j.ps in many longitudinal muscle cells of 8- and 50-week-old: rapid and subsequent slow hyperpolarization. A VIP receptor antagonist sel ectively inhibited the slow hyperpolarization. 5 Exogenously added VIP induced no appreciable change in the membrane poten tial of longitudinal muscle cells of 2-week-old, whereas it induced slight slow hyperpolarization of the cell membrane in 4-week-old and magnitude of the hyperpolarization increased with age. On the other hand, relaxant respo nse of the longitudinal muscle to exogenously added VIP was high in younger rats. 6 The present results suggest that the role of VIP in mediating NANC relaxa tion of longitudinal muscle of the Wistar rat distal colon is very little a t neonatal stage, but it increases with age.