Mimicking of Arginine by Functionalized Nω-Carbamoylated Arginine As a New Broadly Applicable Approach to Labeled Bioactive Peptides: High Affinity Angiotensin, Neuropeptide Y, Neuropeptide FF, and Neurotensin Receptor Ligands As Examples

IntroductionNeuropeptide Y(NPY) has potent antidepressant and orexigenic properties suggesting that altered NPY signaling can be relevant to etiology of altered mood and appetite commonly co-occurring in depressive disorder.ObjectiveStudy if plasma levels and affinities of anti-NPY immunoglobulins(autoAbs) are affected in depression.MethodsPlasma levels of NPY-reactive total/free IgG, IgM and IgA autoAbs were measured by ELISA in 14 patients with mild and in 9 patients with moderate depression and 20 controls. Affinity of autoAbs was assayed by the plasmon resonance. Depressant-like effect of human autoAbs was studied in mice using forced-swim test(FST) after IV injections of patients’ and controls’ IgG. Effects of affinity anti-NPY to antagonize NPY-induced antidepressant and orexigenic effects were studied in mice.ResultsPlasma levels of NPY total IgG autoAbs were lower in patients with moderate depression than in patients with mild depression and healthy controls. MADRS scores correlated negatively with levels of NPY free autoAbs but not with their affinity values were not significantly among study groups. Body mass index(BMI) correlated negatively with affinities of NPY IgG autoAbs. Immobility time in FST was increased by I.V. injection of IgG of patients and controls and correlated negatively with levels of NPY total IgG autoAbs. Low and high affinity NPY IgG autoAbs antagonized NPY-induced anti-immobility effect. Higher affinity autoAbs antagonized more NPY-induced food intake.ConclusionThese data suggest that changes of plasma levels of anti-NPY autoAbs are relevant to altered mood while changes of their affinity may be involved in altered appetite in depressive disorder.

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Neuropeptide Y Receptor Genes Mapped in Human and Mouse: Receptors with High Affinity for Pancreatic Polypeptide Are Not Clustered with Receptors Specific for Neuropeptide Y and Peptide YY

Genomics ◽

10.1006/geno.1997.5024 ◽

1997 ◽

Vol 46 (2) ◽

pp. 287-290 ◽

Cited By ~ 6

Author(s):

C.M. Lutz ◽

J.E. Richards ◽

K.L. Scott ◽

S. Sinha ◽

T.L. Yang-Feng ◽

...

Keyword(s):

Neuropeptide Y ◽

Pancreatic Polypeptide ◽

Peptide Yy ◽

High Affinity ◽

Neuropeptide Y Receptor ◽

Human And Mouse

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Y2 receptors for peptide YY and neuropeptide Y on dispersed chief cells from guinea pig stomach

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1992.262.4.g756 ◽

1992 ◽

Vol 262 (4) ◽

pp. G756-G762

Author(s):

G. Singh ◽

L. Singh ◽

J. P. Raufman

Keyword(s):

Guinea Pig ◽

Neuropeptide Y ◽

Peptide Yy ◽

Camp Production ◽

Chief Cells ◽

High Affinity ◽

Cell Internalization ◽

Pepsinogen Secretion ◽

Guinea Pig Stomach ◽

Dissociation Constant Kd

Peptide YY (PYY) and neuropeptide Y (NPY) inhibit agonist-induced adenosine 3',5'-cyclic monophosphate (cAMP) production and pepsinogen secretion from chief cells. We used radiolabeled PYY and NPY to characterize receptors on chief cells from guinea pig stomach. Binding of 125I-labeled PYY was rapid (70% maximal within 10 min) and specific (not inhibited by secretin, vasoactive intestinal peptide, cholecystokinin, carbachol, prostaglandin E2, forskolin, or cholera toxin). Measurement of the ability of PYY to inhibit binding of 125I-PYY indicated the presence of 1.8 x 10(3) high-affinity [dissociation constant (Kd) = 1.7 nM] and 5.1 x 10(4) low-affinity (Kd = 83.3 nM) sites/cell. Internalization of bound 125I-PYY was suggested by slow and incomplete dissociation in the presence of unlabeled PYY (50% after 2 h) and was examined further by measuring residual binding after washing with acetic acid (pH 2.5), glycine (pH 10.5), or trypsin. After 30 min at 37 degrees C, internalization of radioligand was evidenced by the failure of washing with these solutions to remove 50-65% of bound radioactivity. At 4 degrees C, internalization of 125I-PYY was nearly abolished. Binding of 125I-PYY and 125I-NPY was inhibited by NPY-(13-36) but not by [Leu31,Pro34]NPY indicating that these are Y2 receptors. In guinea pig chief cells, PYY and NPY modulate cAMP-mediated pepsinogen secretion by interacting with specific high-affinity Y2 receptors.

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