Selective increase of dark phase water intake in neuropeptide-Y Y2 and Y4 receptor knockout mice

Abstract

Neuropeptide-Y (NPY) is involved in the regulation of ingestive behaviour and energy homeostasis. Since deletion of the NPY Y2 and Y4 receptor gene increases and decreases food intake, respectively, we examined whether water intake during the light and dark phase is altered in Y2 and Y4 receptor knockout mice. The water consumption of mice staying in their home cages was measured by weighing the water bottles at the beginning and end of the light phase during 4 consecutive days. Control, Y2 and Y4 receptor knockout mice did not differ in their water intake during the light phase. However, during the dark phase Y2 and Y4 receptor knockout mice drank significantly more (46-63 %, P<0.05) water than the control mice. The total daily water intake over 24 h was also enhanced. The enhanced water intake during the dark phase was not altered by the β-adrenoceptor antagonist propranolol or the angiotensin AT1 receptor antagonist telmisartan (each injected intraperitoneally at 10 mg/kg). These data indicate that NPY acting via Y2 and Y4 receptors plays a distinctive role in the regulation of nocturnal water consumption. While β-adrenoceptors and angiotensin AT1 receptors do not seem to be involved, water intake in Y2 and Y4 receptor knockout mice may be enhanced because presynaptic autoinhibition of NPY release and inhibition of orexin neurons in the central nervous system are prevented.

Restriction of Drinking Water Abrogates Splanchnic Vasodilation and Portal Hypertension in Portal Vein-Ligated Rats

“…However, other endogenous mediators such as endothelin-1 or neuropeptide Y have also been found to correct the in vitro mesenteric vascular hyporesponsiveness in portal hypertension [10] and might hence likewise be involved in the beneficial effect of water restriction [34] . In agreement with this notion, neuropeptide Y is reportedly involved in the regulation of water intake and thirst [35] , and [36] dehydration stimulates the endogenous release of endothelin-1 [37] .…”

Neuropeptide Y Y2 receptor in health and disease

“…The proabsorptive effect is obviously carried via Y2 receptors, and is of medical interest in malabsorptive conditions (short bowel syndrome), and in diseases (enterocolitis, cholera, Krohn's disease). Also, deletion of either the Y2 or the Y4 receptor in the mouse was shown to increase the dark‐phase water intake ( Wultsch et al , 2006 ), indicating a decrease in water absorption due to the receptor knockouts. It should be noted that the antisecretory effects of PYY could involve the Y4 and Y1 receptors in addition to the Y2 receptor ( Souli et al , 1997 ).…”

Y4 Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa

“…In addition GR231118, a homodimeric peptide based on the C-terminal sequence of NPY [(Ile, Glu,Pro,Dpr,Tyr,Arg,Leu,Arg,Try-NH 2 )-2-cyclic(2,4Ј),(2Ј,4)-diamide, also known as 1229U91] was originally identified as a competitive Y 1 receptor antagonist with low Y 2 affinity (Daniels et al, 1995;Hegde et al, 1995), but this dimeric nonapeptide also has Y 4 affinity and efficacy (Matthews et al, 1997;Parker et al, 1998;Schober et al, 1998Schober et al, , 2000. The recent generation of Y 4 knockout ( Ϫ/Ϫ ) mice provides the only current alternative to explore the loss of specific function associated with obesity (Sainsbury et al, 2002), cardiac function (Smith-White et al, 2002), and water intake (Wultsch et al, 2006). These studies found that Y 4 Ϫ/Ϫ mice are leaner, have decreased resting heart rate with lower arterial blood pressure, and increased dark phase water intake compared with wild-type (WT) mice.…”