Abstract
In mammals, the principal circadian pacemaker is housed in the hypothalamic suprachiasmatic nuclei (SCN). The SCN exhibit high levels of vasoactive intestinal polypeptide (VIP) immunoreactivity and two of the three VIP receptors, VPAC(2) and PAC(1), are found in the rat SCN. However, the role of VIP in the SCN remains unclear. In this study, we examined the phase-resetting actions of VIP and selective VIP receptor agonists on the electrical activity rhythm of rat SCN neurons in vitro. Application of VIP during the subjective day did not shift the peak in the firing rate rhythm. However, VIP treatment during the early or late subjective night evoked a small phase delay or a large phase advance, respectively. The phase-advancing effect of VIP was reproduced by the novel VPAC(2) receptor agonist RO 25-1553, but not by pituitary adenylate cyclase-activating peptide (a potent PAC(1) receptor agonist), or by [K15,R16,L27]VIP(1-7)/GRF(8-27), a novel, selective VPAC(1) receptor agonist. These data show that VIP phase-dependently phase-resets the rodent SCN pacemaker in vitro, presumably via the VPAC(2) receptor. As the pattern of phase-shifting evoked by VIP and RO 25-1553 resembles the phase-resetting actions of light on rodent behavioural rhythms, these data support a role for VIP and the VPAC(2) receptor in photic entrainment of the rodent circadian pacemaker.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Animals
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Circadian Rhythm / drug effects
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Circadian Rhythm / physiology*
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Circadian Rhythm / radiation effects
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Growth Hormone-Releasing Hormone / analogs & derivatives
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Growth Hormone-Releasing Hormone / pharmacology
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Male
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Neuropeptides / pharmacology
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Peptides, Cyclic / pharmacology
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Photic Stimulation
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Rats
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Rats, Wistar
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Hormone / physiology
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Receptors, Vasoactive Intestinal Peptide / agonists
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Receptors, Vasoactive Intestinal Peptide / physiology*
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Receptors, Vasoactive Intestinal Peptide, Type II
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Receptors, Vasoactive Intestinal Polypeptide, Type I
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Suprachiasmatic Nucleus / drug effects*
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Suprachiasmatic Nucleus / physiology
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Suprachiasmatic Nucleus / radiation effects
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Vasoactive Intestinal Peptide / agonists
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Vasoactive Intestinal Peptide / analogs & derivatives
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Vasoactive Intestinal Peptide / pharmacology
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Vasoactive Intestinal Peptide / physiology*
Substances
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Adcyap1 protein, rat
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Neuropeptides
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Peptides, Cyclic
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Hormone
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Receptors, Vasoactive Intestinal Peptide
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Receptors, Vasoactive Intestinal Peptide, Type II
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Receptors, Vasoactive Intestinal Polypeptide, Type I
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Ro 25-1553
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vasoactive intestinal peptide (1-7)-growth hormone-releasing factor (8-27), lysyl(15)-arginyl(16)-leucyl(27)-
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Vasoactive Intestinal Peptide
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Growth Hormone-Releasing Hormone