Effects of neuromedin-K on the rat hypothalamo-pituitary-adrenal axis

The effects of neuromedin-K (NMK) on the rat hypothalamo-pituitary-adrenal (HPA) axis were studied both in vivo and in vitro. A subcutaneous injection of 1 nmol/100 g NMK evoked a rise in plasma ACTH level at 30 min, increased plasma corticosterone (B) concentration (PBC) at 60 and 120 min, and did not alter plasma aldosterone (ALDO) concentration (PAC). The administration of 3 nmol/100 g NMK induced a rise in plasma ACTH level at 120 min and a drop of PBC at 30 min; it increased PBC and PAC at 60 and 120 min. NMK did not affect basal B secretion of dispersed zona fasciculata/reticularis (ZF/R) cells, but markedly enhanced basal ALDO production by dispersed zona glomerulosa (ZG) cells (minimal and maximal effective concentrations were 10(-9) M and 10(-7) M). Video-imaging analysis showed that NMK (10(-8) M) increased intracellular Ca2+ concentration in dispersed ZG cells, but not in ZF/R ones. These findings indicate that NMK exerts a complex modulatory action on the rat HPA axis: low doses of NMK appear to evoke a transient stimulation of ACTH release, while high doses seem to exert a short-term inhibition of glucocorticoid synthesis followed by the compensatory hypersecretion of ACTH; moreover, elevated doses of NMK also exert a strong ALDO secretagogue action by acting directly on the ZG cells.