TiPS - zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA M ay 2994 lVul.151 Higgs, E. A. (1991) Phnrtuncol. Rezl. 43, 109-141 10 Nozaki, K. et nl. (1993) /. Cereb. Blood Florc~ zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Metnb. 13, 70-79 11 Meller, S. T. and Gebhart, G. F. (1993) Paul 52, 127-136 12 Rand, M. J. (1992) Clin. Exp. Phnrmnrol. Plrysiol. 19, 147-169 13 Iversen, H. K., Olesen, J. and Tfelt- Hansen, P. (1989) Pain 38, 17-24 14 Iversen, H. K., Nielsen, T. H., Garre, K., Tfelt-Hansen, P. and Olesen, J. (1992) Eur. 1. Clin. PJmnnncof. 42, 31-35 15 Iversen, H. K., Holm, S. and Friberg, L. (1989) Ceplrnln!pin 9 (Suppl. lo), 84-85 16 Iversen, H. K. (1992) Cliu. Phnmncol. 77~. 52, 125-133 17 Iversen, H. K. and Olesen, J. (1993) Crphnlaf,qin 13 (Suppl. 131, 82 18 Krabbe,‘k. E. and’kIese& J. (1980) Pnirr 8, 253-259 19 Dahl, A., Russell, D., Nyberg-Hansen, R. and Rootwell, K. (1989) Stroke 20, 173-176 20 21 22 23 24 25 26 27 28 Iversen. H. K., Nielsen, T. 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Nw~. 19, 487-493 Dahl, A., Russell, D., Nyberg-Hansen, R. and Rootwell, K. (1990) Cep/rn/n& 10, 87-94 Krabbe, A. AZ., Henriksen, L. and Olesen. J. (1984) Ct$~nlnlg~n 4, 17-23 Horton, 8. T. (1961) Mnryln~d Mm. /. 10, 178-203 Sicuteri, F. and Nicolodi, M. (1993) in Absfmc~s. 7th World Coqr~ss 01, Pnirl Sefiltle, p. 13, IASP Publications Nichols, F. T. 111et 01. (1990) Stroke 21, 555-559 Koh, J-Y. and Chio. D. W. (1988) J. Nelrrosci. 8, 2153-2163 Dawson, T. M., Dawson. V. L. and Snyder, 5. H. (1992) Au?!: Ncurol. 32, 297-311 europeptide Y effector systems: perspectives for dru development Lars Grundemar and Rolf HAkanson zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFED Neuropeptide Y was isolated in 2982 and has since attracted considerable interest. It is zoidely distributed in central and peripheral neurones and can produce a multitude of biological effects in the brain and the periphery. For example, the peptide has been associated with stimulation of food and water intake, control of mood, and regulation of central autonomic functions. In the periphery, sympathetic neuropeptide Y plays a role as a vasopressor and vasoconstrictor. Neuropeptide Y acts on at least three distinct receptor types, referred to as Y,, Y, and y+ This review by zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFED Lars Grundemar and Rolf HBkanson focuses on some neuropeptide Y-dependent mechanisms that may be imulicated in certain disorders and may be promising targets for drugs active’ at neuropeptide Y receptors. Neuropeptide Y and its receptors are present in many parts of the CNS, and the peptide is co-stored with different transmitters in dif- ferent parts of the brain. Neuro- peptide Y is found in a number of peripheral neurones, including perivascular sympathetic nerve fibres where it co-exists with nor- adrenaline. Peptides in the neuro- peptide Y family, which also in- eludes the hormones peptide YY and pancreatic polypeptide, dis- play a compact tertiary structure consisting of a hairpin-like con- formation that is characterized by extensive hydrophobic inter- actions between an N-terminal polyproline helix and a more C- terminally located B-helix. The hairpin loop carries a C-terminal hexapeptide amide that projects away from the hairpin loop’,‘. L. Crmdwm is nrr Associntr Professor itI r/u Deynrtrrxtrl of Clitlicnl Plwwncolog!y, Lurrd Utriuersily Hospital, S-221 85 Lwuf, md R. Hdknmor~ is R Professor irt t/w Depnrtvrort of P/~nnf~nro/ogyy. UnizwrsiQ of Lmff, Sb;lzqnh?tr 10. S-223 62 Lw~d, Sroederr. Biological effects of neuropeptide Y Ingestive behaviour Neuropeptide Y and peptide YY are among the most powerful stimulants of ingestive behaviour known’, and the role of neuro- peptide Y in the control of food and water intake has attracted considerable attention. Injection of neuropeptide Y into various hypothalamic nuclei stimulates the intake of food (in particular, carbohydrates) and water. The effect on water intake seems to be unrelated to the effect on food intake, and the effect of neuropep- tide Y on food intake is sustained in satiated anir.lals. Endogenous neuropeptide Y is proposed to play an important role in ingestive behaviour since injection of anti- sera to neuropeptide Y (Ref. 3) antisense oligonucleotides directed against mRNA for neuro- peptide Y (Ref. 4) suppresses food intake in rats. Furthermore, it has been demonstrated that the se- cretion of neuropeptide Y from hypothalamic neurones is zyxwvutsrqpon in- creased in food-deprived rats and reduced during the course of eating3,‘. Anxiolysis and sedation Cential administration of neuropeptide Y produces anxio- lytic and sedative effects: neuro- peptide Y evokes an EEG pattern resembling that of sedation and it induces behavioural effects similar to those produced by benzodiazepines’. LOW doses of neurope$ide Y induce anxiolysis, while high doses evoke sedation. The anxiolytic effect of neuropep- tide Y is not secondary to a stimu- lated food intake, since injection of neuropeptide Y into the central nucleus of the amygdala induces