Full amino acid sequence of centrally administered NPY required for maximal food intake response

Central administration of NPY (1-36) potently increases food intake and it has been hypothesized that biological activities of NPY are related to its ability to form an alpha-helix, represented by the fragment NPY (14-31). In this experiment the necessity of N-terminal fragments for increasing food intake was evaluated. Two-h fasted male rats were administered 0, 0.2, 1.0 or 5.0 nmol NPY (1-36) or NPY fragments in 5 microliters saline ICV and intake of lab chow pellets was measured for 22 h. Fragments containing all or part of the polyproline-like helix [NPY (1-8)] antiparallel to the alpha-helix dose-relatedly increased food intake for 4 hours after injection. Five nmol NPY (1-36) and NPY (2-36) increased 4-hour food intake 486 and 219%, respectively (p less than 0.05). Fragments excluding the first 8 amino acids but including all of the alpha-helix also increased food intake, but the response was much reduced. Five nmol NPY (9-36) and NPY (14-36) increased 4-hour food intake 128% (p = 0.02) and 62% (NS), respectively. When all or part of the alpha-helix was excluded, no activity was detected, i.e., NPY (21-36) and NPY (32-36). Substitution of dPro for lPro in position 2 increased potency but not efficacy of NPY since food intake was increased at the 0.2 and 1.0 but not 5.0 nmol doses and the percent increase was not more than to 5 nmol NPY (1-36). Thus the maximum food intake response to NPY requires both C-terminal and N-terminal fragments as well as the alpha-helix.