Anorexic action of a new potential neuropeptide Y antagonist [D-Tyr27,36, D-Thr32]-NPY (27-36) infused into the hypothalamus of the rat.
Neuropeptide Y (NPY) produces a vigorous feeding response in several species when it is injected into hypothalamic structures involved in eating behavior. The purpose of this study was to determine whether a unique carboxy terminal fragment of NPY would alter the pattern of eating induced in the rat either by NPY injected into the hypothalamus or by a 24-h period of food deprivation. In this case, two L-tyrosine residues and one L-threonine residue of the NPY27-36 fragment were transformed to their D-conformation to produce [D-Tyr27,36,D-Thr32]-NPY (27-36), i.e., D-NPY27-36. Guide cannulae for microinjection were implanted stereotaxically just dorsal to the paraventricular nucleus (PVN) or ventromedial hypothalamus (VMH) of 24 adult male Sprague-Dawley rats. Following postoperative recovery, a microinjection of artificial CSF or 1.1 microgram or 3.3 micrograms of a peptide was made directly into the PVN or VMH as follows: native NPY; D-NPY27-36; or [L-Tyr27,36, L-Thr32]-NPY (27-36), i.e., L-NPY27-36. Food intakes were measured at intervals of 0.25, 0.5, 1.1, 2.0, 4.0, and 24 h. When D-NPY27-36 was microinjected at NPY reactive sites in the PVN or VMH of the rat 15 min before a similar microinjection of NPY, the intense eating response induced by the peptide was reduced significantly. Not only was the effect dose dependent, but D-NPY27-36 also augmented the latency to feed. A mixture of the two doses of NPY and D-NPY27-36 injected at the same hypothalamic loci did not attenuate the intake of food but tended to enhance the feeding response in the rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Myers
R D
RD
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Wooten
M H
MH
Ames
C D
CD
Nyce
J W
JW
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005508:Food Deprivation / Q000502:physiology; D007031:Hypothalamus / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000033:anatomy & histology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013238:Stereotaxic Techniques; D014697:Ventromedial Hypothalamic Nucleus / Q000033:anatomy & histology / Q000502:physiology
D001067:Appetite Depressants; D009478:Neuropeptide Y