Distribution of neuropeptide Y Y1 receptors in rodent peripheral tissues

Abstract

Using a sensitive immunohistochemical technique, the localization of neuropeptide Y (NPY) Y1-receptor (Y1R)-like immunoreactivity (LI) was studied in various peripheral tissues of rat. Wild-type (WT) and Y1R-knockout (KO) mice were also analyzed. Y1R-LI was found in small arteries and arterioles in many tissues, with particularly high levels in the thyroid and parathyroid glands. In the thyroid gland, Y1R-LI was seen in blood vessel walls lacking alpha-smooth muscle actin, i.e., perhaps in endothelial cells of capillaries. Larger arteries lacked detectable Y1R-LI. A distinct Y1R-immunoreactive (IR) reticulum was seen in the WT mouse spleen, but not in Y1R-KO mouse or rat. In the gastrointestinal tract, Y1R-positive neurons were observed in the myenteric plexus, and a few enteroendocrine cells were Y1R-IR. Some cells in islets of Langerhans in the pancreas were Y1R-positive, and double immunostaining showed coexistence with somatostatin in D-cells. In the urogenital tract, Y1R-LI was observed in the collecting tubule cells of the renal papillae and in some epithelial cells of the seminal vesicle. Some chromaffin cells of adrenal medulla were positive for Y1R. The problem of the specificity of the Y1R-LI is evaluated using adsorption tests as well as comparisons among rat, WT mouse, and mouse with deleted Y1R. Our findings support many earlier studies based on other methodologies, showing that Y1Rs on smooth muscle cells of blood vessels mediate NPY-induced vasoconstriction in various organs. In addition, Y1Rs in other cells in parenchymal tissues of several organs suggest nonvascular effects of NPY via the Y1R.

Neuropeptide Y Y1 receptor antagonism increases bone mass in mice

“…The Y1 receptor mediates remarkable effects in an extensive variety of important physiologic functions, namely in the regulation of feeding behaviour [20] and [21], energy balance [26] and adiposity [10] and [14], consistent with its wide distribution in central and peripheral tissues [24]. Therefore, an oral delivery of Y1 receptor antagonist might have been expected to induce some additional effects on other physiological systems besides bone.…”

“…Animals maintained a high avidity for jelly throughout the study period. Given the wide peripheral distribution of Y1 receptor in rodents [24], we checked for possible side effects of BIBO3304 by monitoring body weight twice a week at the same time of the day. Body composition changes were also examined using DXA analysis at the fourth and eighth week of treatment.…”

“…In order to avoid stress induced by gavage or transcutaneous delivery, BIBO3304 was incorporated into an artificially flavoured jelly [23] and given to mice that had been trained to eat it on a daily basis for 8 weeks. Due to the wide distribution of Y1 receptors in peripheral tissues [24] and the Y1 receptor-mediated actions in other physiological systems such as energy homeostasis [10], metabolic changes were also monitored throughout the treatment period. butyl]-α-phenyl-benzeneacetamide ditrifluoroacetate (Tocris Bioscience, Bristol, UK) was delivered orally to mice via a novel method previously described [23].…”

Osteoblast specific Y1 receptor deletion enhances bone mass

“…Despite being first characterised as a post-synaptic receptor, the Y1 receptor can also be found pre-synaptically and has a wide distribution both in the central nervous system as well as in the periphery [8] and [9]. Germline Y1 receptor knockout (Y1 −/− ) mice have a high bone mass phenotype with a generalised increase in bone formation on both cortical and cancellous surfaces [3].…”

Neuropeptide Y receptor expression in human primary ovarian neoplasms

“…The Y1 receptor incidence in vessels adjacent to the tumors and in normal ovarian stroma is remarkably high, in agreement with the previous reports of Y1 receptors in vessels in various organs of rats and humans. 26,27 The Y1 receptor incidence in intratumoral vessels appears to be lower. This can be explained by the fact that NPY receptors are expressed in vascular smooth muscle cells that are less prominent in newly formed intratumoral vessels than in normal vessels.…”