Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor–Stimulated Nitric Oxide Production

Bitter taste receptors (T2Rs) are G-protein-coupled receptors (GPCRs) expressed on the tongue but also in various locations throughout the body, including on motile cilia within the upper and lower airways. Within the nasal airway, T2Rs detect secreted bacterial ligands and initiate bactericidal nitric oxide (NO) responses, which also increase ciliary beat frequency (CBF) and mucociliary clearance of pathogens. Various neuropeptides, including neuropeptide tyrosine (neuropeptide Y or NPY), control physiological processes in the airway including cytokine release, fluid secretion, and ciliary beating. NPY levels and/or density of NPYergic neurons may be increased in some sinonasal diseases. We hypothesized that NPY modulates cilia-localized T2R responses in nasal epithelia. Using primary sinonasal epithelial cells cultured at air–liquid interface (ALI), we demonstrate that NPY reduces CBF through NPY2R activation of protein kinase C (PKC) and attenuates responses to T2R14 agonist apigenin. We find that NPY does not alter T2R-induced calcium elevation but does reduce T2R-stimulated NO production via a PKC-dependent process. This study extends our understanding of how T2R responses are modulated within the inflammatory environment of sinonasal diseases, which may improve our ability to effectively treat these disorders.

Surgical denervation of porcine ovaries during the middle luteal phase of the oestrous cycle changes their morphology and steroidogenic activity

Changes in both the morphology and the steroidogenic activity of porcine ovaries denervated surgically on day 12 of the oestrous cycle were studied. Neurectomy of the plexus and the superior ovarian nerves caused a dramatic reduction in the number (or even a disappearance) of dopamine-β-hydroxylase- and/or neuropeptide tyrosine-immunoreactive nerve terminals. On day 20 of the subsequent oestrous cycle, the number of small follicles increased (P < 0.01) and that of large follicles decreased (P < 0.05) in the denervated ovaries, as compared to the controls. Neurectomy led to a decrease in the level of progesterone (P 4 ; P < 0.001) and androstenedione (A 4 ; P < 0.01) in the fluid from small follicles, A 4 (P < 0.001) and testosterone (T; P < 0.05) in the fluid from medium-sized follicles, as well as in the content of all these steroids in the fluid from large-sized follicles (P < 0.001 for P 4 and P < 0.05 for A 4 and T). Denervation also caused a decrease in the content of A 4 (P < 0.01) and T (P < 0.001) in the wall of follicles. Neurectomy resulted in a significant increase in the immunoexpression of cholesterol side-chain cleavage cytochrome P450 in the follicles and a decrease of 3β-hydroxysteroid dehydrogenase. After denervation, plasma levels of LH, P 4 , A 4 , T, oestrone and oestradiol-17β were lower (P < 0.05–0.001) on the particular days of the study than in the control group. Our data revealed that the denervation of ovaries during the middle luteal phase of the oestrous cycle in gilts caused distinct changes in both the morphology and the steroidogenic activity of the organ, confirming an important role of the peripheral nervous system in the control of the gonad in this species.