Article date: March 2004
By: Nina Pronchuk, William F Colmers in Volume 141, Issue 6, pages 1032-1036
Neuropeptide Y (NPY) profoundly enhances feeding when injected intracerebroventricularly, or directly into hypothalamic nuclei, such as the paraventricular nucleus (PVN). Paradoxically, NPY has a reduced action on feeding in obese Zucker rats relative to lean Zucker rats, although the obese rats have much higher levels of hypothalamic NPY expression. GABAergic inputs to a subpopulation of medial parvocellular PVN (mpPVN) neurons are sensitive to NPY. Here, we tested the hypothesis that the blunted eating response to NPY observed in obese Zucker rats will be reflected in a reduced NPY action at mpPVN GABAergic synapses.
‘Blind’ whole‐cell patch‐clamp recordings made from mpPVN neurons in acute brain slices of lean and obese Zucker rats revealed GABAergic inhibitory postsynaptic currents (IPSC) responses which were inhibited by NPY. While the maximum response in the obese Zucker rats was significantly less than in lean Zucker or Sprague–Dawley rats, there was no difference in the EC50.
Experiments using blocking concentrations of Y1‐ or Y5‐receptor antagonists revealed no differences between lean and obese Zucker rats in the contributions of either of these receptors to the total NPY response in mpPVN.
NPY is less effective at the mpPVN GABA synapse in obese than in lean Zucker rats. This is not associated with a change in the proportion of Y1 or Y5 receptors mediating the NPY response, and is consistent with the downregulation of NPY receptors or a reduction in receptor–effector coupling, and with the reduced sensitivity of obese rats to NPY.
Neuropeptide Y (NPY) profoundly enhances feeding when injected intracerebroventricularly, or directly into hypothalamic nuclei, such as the paraventricular nucleus (PVN). Paradoxically, NPY has a reduced action on feeding in obese Zucker rats relative to lean Zucker rats, although the obese rats have much higher levels of hypothalamic NPY expression. GABAergic inputs to a subpopulation of medial parvocellular PVN (mpPVN) neurons are sensitive to NPY. Here, we tested the hypothesis that the blunted eating response to NPY observed in obese Zucker rats will be reflected in a reduced NPY action at mpPVN GABAergic synapses.
‘Blind’ whole‐cell patch‐clamp recordings made from mpPVN neurons in acute brain slices of lean and obese Zucker rats revealed GABAergic inhibitory postsynaptic currents (IPSC) responses which were inhibited by NPY. While the maximum response in the obese Zucker rats was significantly less than in lean Zucker or Sprague–Dawley rats, there was no difference in the EC50.
Experiments using blocking concentrations of Y1‐ or Y5‐receptor antagonists revealed no differences between lean and obese Zucker rats in the contributions of either of these receptors to the total NPY response in mpPVN.
NPY is less effective at the mpPVN GABA synapse in obese than in lean Zucker rats. This is not associated with a change in the proportion of Y1 or Y5 receptors mediating the NPY response, and is consistent with the downregulation of NPY receptors or a reduction in receptor–effector coupling, and with the reduced sensitivity of obese rats to NPY.
British Journal of Pharmacology (2004) 141, 1032–1036. doi:10.1038/sj.bjp.0705699
DOI: 10.1038/sj.bjp.0705699
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