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.
Meyer-Spasche
Alert
A
School of Biological Sciences, University of Manchester, 3.614 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Piggins
Hugh D
HD
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000201:enzymology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014660:Vasoactive Intestinal Peptide; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases