Peptide YY (PYY), an anorectic peptide, is secreted postprandially from the distal gastrointestinal tract. PYY(3-36), the major form of circulating PYY, binds to the hypothalamic neuropeptide Y Y2 receptor (Y2-R) with a high-affinity, reducing food intake in rodents and humans. Additional gastrointestinal hormones involved in feeding, including cholecystokinin, glucagon-like peptide 1, and ghrelin, transmit satiety or hunger signals to the brain via the vagal afferent nerve and/or the blood stream. Here we determined the role of the afferent vagus nerve in PYY function. Abdominal vagotomy abolished the anorectic effect of PYY(3-36) in rats. Peripheral administration of PYY(3-36) induced Fos expression in the arcuate nucleus of sham-operated rats but not vagotomized rats. We showed that Y2-R is synthesized in the rat nodose ganglion and transported to the vagal afferent terminals. PYY(3-36) stimulated firing of the gastric vagal afferent nerve when administered iv. Considering that Y2-R is present in the vagal afferent fibers, PYY(3-36) could directly alter the firing rate of the vagal afferent nerve via Y2-R. We also investigated the effect of ascending fibers from the nucleus of the solitary tract on the transmission of PYY(3-36)-mediated satiety signals. In rats, bilateral midbrain transections rostral to the nucleus of the solitary tract also abolished PYY(3-36)-induced reductions in feeding. This study indicates that peripheral PYY(3-36) may transmit satiety signals to the brain in part via the vagal afferent pathway.

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The complementary 1,omega-thymine, 1,omega-adenine, and 1,omega-(thymine, adenine) bolaamphiphiles, [N,N'-bis[3-(2,4-dihydroxy-5-methylpyrimidine-1-yl)propionyl]1,n-diaminoalkane [T-n-T (n = 10, 11, 12)], N, N'-bis[3-(6-aminopurine-9-yl)propionyl]1,n-diaminoalkane [A-n-A (n = 10, 11, 12)], and N-[3-(2,4-dihydroxy-5-methylpyrimidine-1-yl)propionyl], N'-[3-(6-aminopurine-9-yl)propionyl]1,n-diaminoalkane [T-n-A (n = 10, 11, 12)], respectively] have been synthesized. The spontaneous homo- and heteroassembly of these nucleobase-based bolaamphiphiles has been studied by light microscopy, energy-filtering transmission electron microscopy, FT-IR, and powder X-ray diffraction analyses. The achiral T-10-T bolaamphiphile produced in 10% ethanolic/aqueous solutions unprecedented double-helical ropes of 1-2 microm in widths and several hundred micrometers in length, whereas the complementary homologue A-10-A gave only microcrystalline solids of 1-10 microm in size. In contrast, an equimolar mixture of T-10-T and A-10-A yielded supramolecular fibers of 15-30 nm in width. (1)H NMR, CD, and UV studies of solution photoreactions of T-10-T suggested that under natural light the chiral rope formation is triggered by photodimerization of trace amounts of the thymine moieties in the T-10-T assemblies. Complementary hydrogen bond formation between the thymine-adenine heterobase pairs was found to prevent such a photoreaction and resulted in no chiral rope formation. The heteroditopic T-12-A bolaamphiphile self-assembled to form supramolecular fibers. Multilamellar organization was proposed for the homo- and heteroassemblies made of T-n-T and A-n-A.

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