TY - JOUR
T1 - Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys
AU - Larsen, Philip Just
AU - Tang-Christensen, M.
AU - Stidsen, C. E.
AU - Madsen, K.
AU - Smith, M. S.
AU - Cameron, J. L.
PY - 1999
Y1 - 1999
N2 - The orexigenic role of central neuropeptide Y (NPY) in nonhuman primates has been questioned. Therefore, we have studied the effect of central NPY on feeding in ad libitumfed male rhesus macaques. NPY dose-dependently increased food intake, with the maximal effect obtained by 50 μg (960 min food intake ± SEM, 104 ± 5 to 188 ± 11 g; vehicle vs. NPY; n = 6). Blood glucose levels were unaffected by intracerebroventricular administration of NPY, but animals receiving either 20 or 50 μg displayed increased plasma levels of insulin and cortisol at few time points. To assess the pharmacological specificity of this response, a novel Y1 antagonist, [(Ile,Glu,Pro,Daba,Tyr,Arg,Leu,Arg,Tyr-NH2)2 cyclic (2,4'),(2',4)-diamide] (Y1(ANT)), was synthesized. Receptor binding experiments demonstrated that Y1(ANT) preferentially binds to Y1 and Y4 receptors (pK(i) 10.12 ± 0.06 and 9.11 ± 0.05 nmol/L, respectively). Functional analysis revealed that Y1(ANT) is a Y1 antagonist and a partial Y4 agonist. Central administration of Y1(ANT) blocked NPY-induced feeding. In food-deprived monkeys, Y1(ANT) attenuated the feeding response. However, Y1(ANT) had no effect on food intake in satiated monkeys. Thus, endogenous NPY is likely to be involved in the regulation of food intake in the nonhuman primate, and this effect is at least partially mediated via Y1-like receptors.
AB - The orexigenic role of central neuropeptide Y (NPY) in nonhuman primates has been questioned. Therefore, we have studied the effect of central NPY on feeding in ad libitumfed male rhesus macaques. NPY dose-dependently increased food intake, with the maximal effect obtained by 50 μg (960 min food intake ± SEM, 104 ± 5 to 188 ± 11 g; vehicle vs. NPY; n = 6). Blood glucose levels were unaffected by intracerebroventricular administration of NPY, but animals receiving either 20 or 50 μg displayed increased plasma levels of insulin and cortisol at few time points. To assess the pharmacological specificity of this response, a novel Y1 antagonist, [(Ile,Glu,Pro,Daba,Tyr,Arg,Leu,Arg,Tyr-NH2)2 cyclic (2,4'),(2',4)-diamide] (Y1(ANT)), was synthesized. Receptor binding experiments demonstrated that Y1(ANT) preferentially binds to Y1 and Y4 receptors (pK(i) 10.12 ± 0.06 and 9.11 ± 0.05 nmol/L, respectively). Functional analysis revealed that Y1(ANT) is a Y1 antagonist and a partial Y4 agonist. Central administration of Y1(ANT) blocked NPY-induced feeding. In food-deprived monkeys, Y1(ANT) attenuated the feeding response. However, Y1(ANT) had no effect on food intake in satiated monkeys. Thus, endogenous NPY is likely to be involved in the regulation of food intake in the nonhuman primate, and this effect is at least partially mediated via Y1-like receptors.
UR - http://www.scopus.com/inward/record.url?scp=0033304541&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033304541&partnerID=8YFLogxK
U2 - 10.1210/jc.84.10.3781
DO - 10.1210/jc.84.10.3781
M3 - Article
C2 - 10523030
AN - SCOPUS:0033304541
SN - 0021-972X
VL - 84
SP - 3781
EP - 3791
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 10
ER -