Vasoactive intestinal polypeptide phase-advances the rat suprachiasmatic nuclei circadian pacemaker in vitro via protein kinase A and mitogen-activated protein kinase.

The firing activity of suprachiasmatic nuclei (SCN) neurones in vitro shows a circadian rhythm with the peak in average firing frequency during the middle of the projected day. Vasoactive intestinal polypeptide (VIP), which is abundant in the rat SCN, phase-advances the time of peak in SCN neuronal activity when applied in vitro during the late projected night; an effect most likely mediated via the VPAC(2) receptor. Employing extracellular single-unit electrophysiology, we investigated the influence of protein kinase A (PKA) inhibitor KT5720 or mitogen-activated protein kinase kinase (MAPKK) inhibitor U0126 on phase advances evoked during the late projected night by VIP or Ro 25-1553, a VPAC(2) receptor agonist. Both inhibitors blocked VIP or Ro 25-1553-induced phase advances, indicating that the late-night resetting actions of VIP via the VPAC(2) receptor require PKA and MEK.