Abstract
The general aim of these studies was to further elucidate the role of NPY receptors in the regulation of the food intake and energy homeostasis, nociception, and inflammation. We have utilized both normal and genetically modified mice, and a number of different techniques to study these mechanisms.
To identify the role of the Y2 receptor subtype in the central control of food intake, Y2 receptor null mutant mice were used. Y2 receptor deficient mice exhibited increased body weight associated with increased food intake and reduced energy expenditure compared to wild type mice.
A possible physiological role for NPY receptors in pain transmission was studied by analysing Y1 and Y2 receptor deficient mice. Y1 receptor mutant mice exhibited increased sensitivity to acute thermal, mechanical, and chemical nociception, as well as neuropathic pain. Y2 receptor mutant mice also exhibited increased sensitivity to acute pain. Capsaicin-induced plasma extravasation, and substance P release was absent in Y1 deficient mice. Peripheral inflammation was not affected in Y2 receptor mutant mice. In addition, we studied the participation of NPY and Y1 receptor in a rodent model of inflammatory bowel disease, using Y1 receptor deficient mice. Clinical manifestation of the disease was attenuated in Y1 mutant mice. Histological analysis also showed that the intestinal tissue damage was reduced in Y1 deficient mice.
The data presented in this thesis suggest that: i) The Y2 receptor plays an important role in the basal control of food intake; ii) Both Y1 and Y2 receptors are involved in nociception, where the Y1 receptor is the predominant NPY receptor mediating the anti-nociceptive effects of NPY; iii) The Y1 receptor is required for neurogenic inflammation, and is involved in intestinal inflammation.
