The NPY Y1 receptor antagonist BIBP 3226 blocks NPY induced feeding via a non-specific mechanism.
We have previously shown that intracerebroventricular BIBP 3226 inhibits NPY induced feeding in rats. However, this was associated with abnormal behaviour, likely to be due to interaction with Y1 receptors involved in mechanisms other than the control of food intake. In order to minimise such interactions we investigated the effects of paraventricular nucleus (PVN) injections of BIBP 3226 and its inactive enantiomer BIBP 3435. Intra-PVN injection of NPY (0.1-2.5 nmol/animal) increased food intake, with an EC50 of approximately 0.15 nmol/animal. Injections of BIBP 3226 and BIBP 3435 (0.25-25 nmol) reduced NPY-induced food intake in a dose responsive manner, with BIBP 3226 reducing food intake by 95%, and BIBP 3435 by 65% at the highest dose tested. The reversibility of the effect of BIBP 3226 was investigated by measuring the feeding response to NPY (0.5 nmol) in animals 1 week after BIBP 3226 injection. The response to NPY was less in animals which had received high doses of BIBP 3226. Animals previously injected with saline vehicle alone showed a normal NPY feeding response. These results suggest that BIBP 3226 may be inhibiting NPY-induced food intake in a non-specific manner, not secondary to inhibition of the Y1 receptor. This does not, however rule out a role for the Y1 receptor in the control of food intake by NPY.
Morgan
D G
DG
ICSM Endocrine Unit at the Hammersmith Hospital, Francis Fraser Labs., London, UK.
Small
C J
CJ
Abusnana
S
S
Turton
M
M
Gunn
I
I
Heath
M
M
Rossi
M
M
Goldstone
A P
AP
O'Shea
D
D
Meeran
K
K
Ghatei
M
M
Smith
D M
DM
Bloom
S
S
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D007267:Injections; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000502:physiology; D013237:Stereoisomerism
C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine