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

Abstract

Changes in participation of vasoactive intestinal peptide (VIP) in nonadrenergic noncholinergic (NANC) relaxation of longitudinal muscle of the distal colon with age were studied in 2- to 50-week-old Wistar rats in vitro. The extent of the VIP-mediated component of the relaxation induced by electrical field stimulation (EFS) was determined by the effect of VIP(10 - 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 gradually increase with age and reached the maximum extent 66% at 50-week-old. Since our previous results suggest that VIP induces NANC relaxation via activation of charybdotoxin (ChTx, a blocker of large conductance Ca(2+)-activated K(+) channel)-sensitive K(+) channels with concomitant slow hyperpolarization in the muscle cells, we next studied whether ChTx-sensitive component and slow hyperpolarization changes with age. Extent of ChTx-sensitive component of the relaxation increased with age, showing a very similar pattern to VIP-mediated one. EFS induced monophasic inhibitory junction potentials (i.j.ps) in longitudinal muscle cells of the distal colon of 2- and 4-week-old. EFS also induced biphasic i.j.ps in many longitudinal muscle cells of 8- and 50-week-old: rapid and subsequent slow hyperpolarization. A VIP receptor antagonist selectively inhibited the slow hyperpolarization. Exogenously added VIP induced no appreciable change in the membrane potential 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 response of the longitudinal muscle to exogenously added VIP was high in younger rats. The present results suggest that the role of VIP in mediating NANC relaxation of longitudinal muscle of the Wistar rat distal colon is very little at neonatal stage, but it increases with age.