Deletion of the neuropeptide Y (NPY) Y1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

C Cavadas, D Céfai… - Proceedings of the …, 2006 - National Acad Sciences
C Cavadas, D Céfai, J Rosmaninho-Salgado, MA Vieira-Coelho, E Moura, N Busso…
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
The contribution of neuropeptide Y (NPY), deriving from adrenal medulla, to the
adrenosympathetic tone is unknown. We found that in response to NPY, primary cultures of
mouse adrenal chromaffin cells secreted catecholamine, and that this effect was abolished
in cultures from NPY Y1 receptor knockout mice (Y1−/−). Compared with wild-type mice
(Y1+/+), the adrenal content and constitutive release of catecholamine were increased in
chromaffin cells from Y1−/− mice. In resting animals, catecholamine plasma concentrations …
The contribution of neuropeptide Y (NPY), deriving from adrenal medulla, to the adrenosympathetic tone is unknown. We found that in response to NPY, primary cultures of mouse adrenal chromaffin cells secreted catecholamine, and that this effect was abolished in cultures from NPY Y1 receptor knockout mice (Y1−/−). Compared with wild-type mice (Y1+/+), the adrenal content and constitutive release of catecholamine were increased in chromaffin cells from Y1−/− mice. In resting animals, catecholamine plasma concentrations were higher in Y1−/− mice. Comparing the adrenal glands of both genotypes, no differences were observed in the area of the medulla, cortex, and X zone. The high turnover of adrenal catecholamine in Y1−/− mice was explained by the enhancement of tyrosine hydroxylase (TH) activity, although no change in the affinity of the enzyme was observed. The molecular interaction between the Y1 receptor and TH was demonstrated by the fact that NPY markedly inhibited the forskolin-induced luciferin activity in Y1 receptor-expressing SK-N-MC cells transfected with a TH promoter sequence. We propose that NPY controls the release and synthesis of catecholamine from the adrenal medulla and consequently contributes to the sympathoadrenal tone.
National Acad Sciences