Hypothalamic administration of cAMP agonist/PKA activator inhibits both schedule feeding and NPY-induced feeding in rats.
Following central administration, neuropeptides that decrease the level of cAMP induce feeding. Conversely, cAMP activating neuropeptides tend to elicit satiety. When the inhibitory effect of neuropeptide Y (NPY) on the hypothalamic cAMP production was blocked by pertussis toxin, the potent orexigenic effect of NPY was lost. These findings suggest that there may be a link between hypothalamic cAMP and the central regulation of food intake. In this report, we show that the injection of the membrane-permeable cAMP agonist, adenosine-3',5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMP), into perifornical hypothalamus (PFH) significantly inhibited schedule-induced and NPY-induced food intake for up to 4h. This inhibitory effect was normalized within 24h. A taste aversion could not be conditioned to Sp-cAMP treatment, suggesting that the anorectic response was not due to malaise. Sp-cAMP administration significantly increased the active protein kinase A (PKA) activity in dorsomedial (DMH) and ventromedial (VMH), but not in lateral (LH) hypothalamus. Consistently, food deprivation lowered, while refeeding normalized endogenous cAMP content in DMH and VMH, but not in LH areas. No significant effect of adenosine-3',5'-cyclic monophosphorothioate Rp-isomer (Rp-cAMP, cAMP antagonist) was observed on hypothalamic PKA activity, schedule-induced, or NPY-induced food intake. These findings suggest that the increase in cAMP level and PKA activity in DMH and VMH areas may trigger a satiety signal.
Sheriff
Sulaiman
S
Department of Surgery, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, 45267, Cincinnati, OH, USA. sherifs@email.uc.edu
Chance
William T
WT
Iqbal
Sabahat
S
Rizvi
Tilat A
TA
Xiao
Chun
C
Kasckow
John W
JW
Balasubramaniam
A
A
D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004435:Eating / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D009478:Neuropeptide Y; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases