Time course of short-term and long-term orexigenic effects of Agouti-related protein (86-132)

Agouti-related protein (AGRP) is a newly identified orexigenic peptide that acts as an endogenous antagonist of melanocortin receptors MC3 and MC4. The present study examined the time course of the orexigenic effects of synthetic AGRP (86-132). Intracerebroventricular infusion of 0.1 nmol AGRP (86-132) increased food intake by 450 ± 81% at 2 h post-injection. A second increase in non-cumulative food intake (512 ± 135%) was observed at 6 h post-injection. Following a single dose of AGRP (86-132) (0.1 nmol) the increased food intake was sustained for 6 days, occurring in the light cycle of the first 2 days and subsequently switching to the dark cycle of the last 4 days. These time course profiles indicate the complexity of the mechanisms involved in AGRP-induced feeding.

[1]  R. Cone,et al.  A Unique Metalolic Sysdrone Causes Obesity in the Melanocortin-3 Receptor-Deficient Mouse. , 2000, Endocrinology.

[2]  M. Wirth,et al.  Agouti-related protein in the hypothalamic paraventricular nucleus: effect on feeding , 2000, Peptides.

[3]  D. Smith,et al.  Hypothalamic localization of the feeding effect of agouti-related peptide and alpha-melanocyte-stimulating hormone. , 2000, Diabetes.

[4]  L. Yaswen,et al.  Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin , 1999, Nature Medicine.

[5]  G. Barsh,et al.  Physiological and anatomical circuitry between Agouti-related protein and leptin signaling. , 1999, Endocrinology.

[6]  C. Mobbs,et al.  Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. , 1999, Endocrinology.

[7]  M. Tota,et al.  Molecular interaction of Agouti protein and Agouti-related protein with human melanocortin receptors. , 1999, Biochemistry.

[8]  S. Bloom,et al.  A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. , 1998, Endocrinology.

[9]  V. Katta,et al.  Determination of disulfide structure in agouti-related protein (AGRP) by stepwise reduction and alkylation. , 1998, Biochemistry.

[10]  A. Grüters,et al.  Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans , 1998, Nature Genetics.

[11]  W. Sadee,et al.  A synthetic human Agouti‐related protein‐(83–132)‐NH2 fragment is a potent inhibitor of melanocortin receptor function , 1998, FEBS letters.

[12]  G. Barsh,et al.  Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. , 1997, Science.

[13]  R. Cone,et al.  Targeted Disruption of the Melanocortin-4 Receptor Results in Obesity in Mice , 1997, Cell.

[14]  H. Akil,et al.  Evidence that β-endorphin is synthesized in cells in the nucleus tractus solitarius: detection of POMC mRNA , 1992, Brain Research.

[15]  H. Akil,et al.  In Vitro release of hypothalamic β-endorphin βE by arginine vasopressin, corticotropin-releasing hormone and 5-hydroxytryptamine: Evidence for release of opioid active and inactive βE forms , 1990, Neuropeptides.

[16]  G. Bray,et al.  Acetylation alters the feeding response to MSH and beta-endorphin , 1989, Brain Research Bulletin.

[17]  A. Vergoni,et al.  ACTH-(1–24) and α-MSH antagonize feeding behavior stimulated by kappa opiate agonists , 1986, Peptides.

[18]  M. E. Lewis,et al.  Proopiomelanocortin peptide immunocytochemistry in rhesus monkey brain , 1984, Brain Research Bulletin.

[19]  L. Swanson.  The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[20]  H. Akil,et al.  Opiate binding properties of naturally occurring N- and C-Terminus modified beta-endorphins , 1981, Peptides.

[21]  C. Sandman,et al.  Endorphin analogs with potent and long-lasting analgesic effects , 1977, Pharmacology Biochemistry and Behavior.

[22]  R. G. Browne,et al.  beta-Endorphin: endogenous opiate or neuroleptic? , 1977, Science.

[23]  H. Loh,et al.  beta-endorphin is a potent analgesic agent. , 1976, Proceedings of the National Academy of Sciences of the United States of America.