Interaction of neuropeptide Y and corticotropin-releasing factor signaling pathways in AR-5 amygdalar cells.
Corticotropin-releasing factor (CRF) is a 41 amino acid neuropeptide which is involved in the stress response. CRF and neuropeptide Y (NPY) produce reciprocal effects on anxiety in the central nucleus of the amygdala. The molecular mechanisms of possible CRF-NPY interactions in regulating anxiety behavior is not known. In the central nervous system, the action of NPY leads to inhibition of cAMP production while CRF is known to stimulate levels of cAMP in the brain. Consequently, we hypothesized that NPY may antagonize anxiety-like behavior by counter-regulating CRF-stimulated cAMP accumulation and activation of the protein kinase A pathway. We have engineered an immortalized amygdalar cell line (AR-5 cells) which express via RT-PCR, the CRF(2alpha), Y(1) and Y(5) NPY receptor. In addition, in these cells CRF treatment results in significant concentration-dependent increases in cAMP production. Furthermore, incubation of 3 microM CRF with increasing concentrations of NPY was able to significantly inhibit the increases in cAMP compared to that observed with 3 microM CRF treatment alone. These findings suggest that CRF and NPY may counter-regulate each other in amygdalar neurons via reciprocal effects on the protein kinase A pathway.
Sheriff
S
S
University of Cincinnati College of Medicine, Department of Surgery, Cincinnati, OH 45267, USA.
Dautzenberg
F M
FM
Mulchahey
J J
JJ
Pisarska
M
M
Hauger
R L
RL
Chance
W T
WT
Balasubramaniam
A
A
Kasckow
J W
JW
D000679:Amygdala / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D009478:Neuropeptide Y / Q000378:metabolism*; D011485:Protein Binding; D017476:Receptors, Neuropeptide Y; D015398:Signal Transduction
D017931:DNA Primers; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP