Agonists for neuropeptide Y receptors Y1 and Y5 stimulate different phases of feeding in guinea pigs.
1. The stimulatory effect of neuropeptide Y (NPY) on food intake is well established but the roles of the receptor subtypes Y(1) and Y(5) have been difficult to define. We have studied the effects of two novel Y(1)-preferring and two Y(5)-preferring agonists on feeding in guinea pigs. 2. The Y(1)-preferring receptor agonists [Arg(6),Pro(34)]pNPY and [Phe(7),Pro(34)]pNPY had high affinity for the Y(1) receptor (K(i) values 0.07 and 0.04 nM, respectively) and nanomolar affinity for the Y(5) receptor. Administration of either compound into the third brain ventricle increased food intake equally to NPY. 3. The Y(5) agonist [Ala(31),Aib(32)]pNPY displayed a moderate affinity for the Y(5) receptor (K(i) 7.42 nM) and a low affinity for Y(1) (K(i) 1.7 micro M). This compound had only a modest effect on feeding. 4. The other Y(5)-preferring peptide [cPP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]hPP had a higher affinity at the Y(5) receptor (K(i) 1.32 nM) and also at the Y(1) receptor (K(i) 85 nM). It potently stimulated feeding: the food consumption after administration of this peptide was two-fold compared to NPY. 5. Our results support the view that both the receptor subtypes Y(1) and Y(5) are involved in the stimulation of feeding. As the action profiles of the Y(1) and Y(5) agonists on feeding parameters were different, it seems that they influence different phases of eating.
Lecklin
Anne
A
Department of Neuroscience, Unit of Pharmacology, Uppsala University, Box 593, S-75124 Uppsala, Sweden. anne.lecklin@uku.fi
Lundell
Ingrid
I
Salmela
Suvi
S
Männistö
Pekka T
PT
Beck-Sickinger
Annette G
AG
Larhammar
Dan
D
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D005247:Feeding Behavior / Q000187:drug effects*; D006168:Guinea Pigs; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000819:agonists* / Q000378:metabolism
D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor