Distribution of peripherally injected peptide YY ([I-125] PYY (3-36)) and pancreatic polypeptide ([I-125] hPP) in the CNS: enrichment in the area postrema

The mechanism by which blood-bome peptide YY (3-36) (PYY(3-36)) and pancreatic polypeptide (PP) inhibit food intake is not clear and could implicate peripheral (vagal afferent pathways) and/or central (direct action on specific brain nuclei) mechanisms. To identify the primary brain structure(s) that could be activated after a peripheral injection of neuropeptide Y-related peptides, we investigated the distribution of radioactive materials using whole body autoradiography and coronal brain sections. Rats were injected with [1251] porcine (p) PYY(3-36) (i.p., 10 mu Ci) and killed after 30 min, 1, 2, or 4 h. After i.p. administration, significant amounts of radioactive materials were rapidly (<30 min) detected in the blood circulation and various tissues including the kidneys, liver, lung, heart, bone marrow, gastrointestinal tract, and thyroid gland, whereas in the brain, low but significant amounts of radioactive materials were detected at the level of the area postrema. Next, we investigated the distribution of radioactive labeling in the brain after i.v. injections of [I-125] pPYY(3-36) (Y-2 and Y-5 subtypes), [I-125] human (h) PP (Y-4 and Y-5 receptors), and [I-125] [Leu(31), pro(34)] (p)pyy (Y-1, Y-4 and Y-5 classes) in the rat brain. Fifteen minutes post injection, autoradiograms revealed positive signals only in the area postrema after the injection of [I-125]-hPP and [I-125] [Leu(31), pro(34)]ppyy. Whereas the presence of [I-125]ppyy (3-36)-related labeling was detected in the area postrema, subfornical organ, and median eminence. In all other brain structures, including all hypothalamic nuclei and other circumventricular organs, near background level signals were detected. These data suggest that the inhibition of food intake observed after peripheral injections of pPYY(336) and hPP could involve receptor activation preferentially located at the level of the area postrema, a structure wellknown to be involved in the modulation of food intake.