Acute effects of antisense antagonism of a single peptide
neurotransmitter in the circadian clock.
Scarbrough, Kathryn, Jacob P. Harney, Katherine L. Rosewell, and
Phyllis M. Wise.
University of Kentucky College of Medicine, Department of
Physiology, Lexington, KY 40536
APStracts 2:0233R, 1995.
The circadian clock that resides in the suprachiasmatic nucleus (SCN)
of the hypothalamus is the major neural pacemaker driving most 24 h
rhythms in mammals. Several neurotransmitter peptides are synthesized
within this nucleus and communicate rhythmically with other cells in
the SCN as well as with cells in other regions of the brain. At the
present time, little is known about their role in regulating outputs
of the clock. We demonstrate that antisense oligodeoxynucleotides
corresponding to the NH2-terminus and the translation start site of
vasoactive intestinal peptide (VIP) infused into the suprachiasmatic
region of rats temporarily abolishes the circadian rhythm of
corticosterone secretion without influencing stress-related
corticosterone secretion in the same animals. Levels of VIP peptide
are suppressed 30% on the second day following antisense treatment.
These results indicate that a single neuropeptide transmitter in the
circadian clock may serve a distinct role in the control of specific
circadian rhythms.
Received 15 March 1995; accepted in final form 7 August 1995.
APS Manuscript Number R171-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.