Neuropeptide Y receptor

Neuropeptide Y receptors are a class of G-protein coupled receptors which are activated by the closely related peptide hormones neuropeptide Y, peptide YY and pancreatic polypeptide. These receptors are involved in the control of a diverse set of behavioral processes including appetite, circadian rhythm, and anxiety.

1068148-47-9
1094873-14-9
JNJ-31020028
1094873-14-9
113662-54-7
Antagonist G
115150-59-9
123583-37-9
125580-28-1
Peptide YY (3-36)
126339-09-1
132699-73-1
CYM 9484
1383478-94-1
Galantide
138579-66-5
M40
143896-17-7
153549-84-9
GR 231118
158859-98-4
PD 160170
181468-88-2

Background


Neuropeptide Y (NPY), Peptide YY (PYY), and Pancreatic Polypeptide (PP) bind to six identified/cloned mammalian receptors, Y1-y6. Of these, only the Y3 receptor has not been be cloned. In humans, the Y1-Y5 receptors are functional, but y6, is a non-functional truncated receptor and therefore is designated with a lowercase y. NPY receptors belong to the rhodopsin-like superfamily (class I) of G-protein-coupled receptors (GPCRs). Prominent features are: seven transmembrane (TM) helices, two (in Y2&Y5) to four (in Y1, Y4 &y6) extracellular cystein residues (potential sites of disulfide bonds), one (in Y2&Y5) or several (three in Y1&Y4) consensus sites for N-linked glycosylation, one cysteine in the cytoplasmic tail (possible site for anchorage to the cell membrane), and a highly conserved a-helix immediately after the last transmembrane region, TM 7. Of the six NPY receptors, Y1, Y4 and y6 show more homology and similarities in structure than do Y2 and Y5 receptors.

The Y1 receptor Function

Y1 receptors in the brain have been found to participate in stimulation of food intake, antinociception, centrally-mediated reduction of blood pressure and heart rate, anxiolysis, antidepression, sedation, and ethanol consumption. In some populations, such as Pima Indians, the Yl receptor polymorphism was found to be associated with morbid obesity, while in others, such as French Caucasians, no such association was observed. In the cardiovascular system, NPY stimulates vasoconstriction and smooth muscle cell growth in vitro, Most recently, postangioplasty carotid artery occlusion and atherosclerosis in rats are found to be mediated via the Y1 receptor.

The Y2 receptor Functions

Inhibition of neurotransmitter release, such as NPY, catecholamines, and glutamate are the known Y2 receptor functions in the central and the peripheral nervous system. Consequently, some of the Y2 receptor actions are opposite of those of Y1’s: e.g. anxiogenesis, centrally-mediated increase in blood pressure and heart rate, and induction of satiety. Some of the other centrally-mediated Y2 receptor actions are: decreased stress coping ability, circadian rhythm shifts, increased bone density and volume, memory retention, and epilepsy, In the periphery, Y2 receptor activation has been linked to gastrointestinal functions, and NPY-mediated angiogenesis.

Y3 Receptor Functions

Hypotension and bradycardia induced by central administration of NPY, vasodialation in the lungs and rat aortic endothelial cells, catecholamine secretion from human adrenal chromaffin cells, and stimulation of cardiac muscle contractility are reported functions of the Y3-receptor.

The Y4 Receptor Functions

Regulation of gut motility and secretion has long been attributed to the Y4 receptor, However, more recently, studies of Y4 deficient transgenic mice has unraveled some of the centrally mediated functions of this receptor. Among these are restored fertility in Y4 deficient obese mice {Y4 (-/-), ob/ob}, which is suggestive of an inhibitory role of this receptor on reproduction under high NPY-ergic activity; and, a synergistic action between Y2 and Y4 receptors in reducing adiposity and increasing bone mass, seen in Y2/Y4 double knockout {Y2 (-/-), Y4 (-/-)} mice. Moreover, in the cardiovascular system, inhibition of neurogenic vasoconstriction of rat renal, femoral and tail arteries are also attributed to the Y4 receptor.

The Y5 receptor Functions

Originally, the Y5 receptor was believed to be the exclusive hypothalamic receptor mediating NPY-stimulated food intake, However, following binding and receptor knockout studies, it became apparent that Y1, Y2, and even Y4 receptors can participate in the feeding response. Y1 and Y5 receptors seem to cooperate in many of the centrally mediated effects of NPY, including stimulation of feeding, antiepileptic activity, modulation of the circadian rhythm, regulation of metabolism, and last but not least, modulation of the hypothalamo-pituitary axis. Peripherally, the Y5 receptor is implicated in modulation of the immune system and in various cardiovascular effects of NPY. Facilitation of sympathetically-stimulated leukocytosis by the Y5 receptor and its inhibition via the Y1 receptor have recently been recognized as immune functions of these receptors, In the cardiovascular system, Y5 is found to mediate NPYinduced cardiomyocyte hypertrophy subsequent to pressure overload in the heart. Moreover, synergistically with the Yl receptor, Y5 participates in stimulation of smooth muscle cell growth in vitro. In vivo, Y5 receptor expression is induced in blood vessels succeeding tissue ischemia or injury, leading to angiogenesis in collaboration with the Y2 receptor, and atherosclerosis-like plaque generation in cooperation with the Y1 receptor.

Reference:

Movafagh, S. (2005). Neuropeptide Y receptor subtype (s) mediating migration, proliferation, and differentiation of endothelial cells in vitro, and angiogenesis in vivo.