Further characterization of neuropeptide Y receptor subtypes using centrally truncated analogs of neuropeptide Y: evidence for subtype-differentiating effects on affinity and intrinsic efficacy.
Previous attempts to classify neuropeptide Y receptor subtypes suffered from relying only on carboxyl-terminal analogs and fragments of neuropeptide Y. We have tested the potency and affinity of chemically different compounds, i.e., centrally truncated analogs of neuropeptide Y, in three Y1-like (Ca2+ mobilization in HEL cells, blood pressure increases in pithed rats, and 125I-neuropeptide Y binding in SK-N-MC cells) and two Y2-like (125I-neuropeptide Y binding to rabbit kidney membranes and presynaptic inhibition in rat vas deferens) model systems of neuropeptide Y receptors. Our data confirm the concept of two major subclasses of neuropeptide Y receptors, with some centrally truncated neuropeptide Y analogs having high affinity for Y2-like and low affinity for Y1-like neuropeptide Y receptors. Some of the truncated neuropeptide Y analogs are antagonists at Y1-like receptors and (possibly partial) agonists at Y2-like receptors. Our data also indicate that amino acid residues distal from the amino- and carboxyl-terminal ends of the peptide may subtype-selectively affect affinity and intrinsic efficacy of peptide agonists at neuropeptide Y receptors.
Michel
M C
MC
Department of Medicine, University of Essen, Germany.
Gaida
W
W
Beck-Sickinger
A G
AG
Wieland
H A
HA
Doods
H
H
Dürr
H
H
Jung
G
G
Schnorrenberg
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D002118:Calcium