Agonists for neuropeptide Y receptors Y[sub1] and Y[sub5] 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[SUB1] and Y[SUB5] have been difficult to define. We have studied the effects of two novel Y[SUB1]-preferring and two Y[SUB5]-preferring agonists on feeding in guinea pigs. 2. The Y[SUB1]-preferring receptor agonists [Arg[SUP6],Pro[SUP34]]pNPY and [Phe[SUP7],Pro[SUP34]]pNPY had high affinity for the Y[SUB1] receptor (K[SUBi] values 0.07 and 0.04 nM, respectively) and nanomolar affinity for the Y[SUB5] receptor. Administration of either compound into the third brain ventricle increased food intake equally to NPY. 3 The Y[SUB5] agonist [Ala[SUP31],Aib[SUP32]pNPY displayed a moderate affinity for the YSUB5] receptor (K[SUBi] 7.42 nM) and a low affinity for Y[SUB1] (K[SUBi] 1.7 μM). This compound had only a modest effect on feeding. 4 The other Y[SUB5]-preferring peptide [cPP[SUP1-7],NPY[SUP19-23],Ala[SUP31],Aib[SUP32],Gln[SUP34]]hPP had a higher affinity at the Y[SUB5] receptor (K[SUBi] 1.32 nM) and also at the Y[SUB1] receptor (K[SUBi] 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[SUB1] and Y[SUB5] are involved in the stimulation of feeding. As the action profiles of the Y[SUB1] and Y[SUB5] agonists on feeding parametric were different, it seems that they influence different phase of eating. [ABSTRACT FROM AUTHOR]