EFFECTS OF NEUROMEDIN-K ON THE RAT HYPOTHALAMOPITUITARY-ADRENAL AXIS

The effects of neuromedin-K (NMK) on the rat hypothalamo-pituitary-adr enal (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 3 0 min, increased plasma corticosterone (B) concentration (PBC) at 60 a nd 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 a nd PAC at 60 and 120 min. NMK did not affect basal B secretion of disp ersed zona fasciculata/reticularis (ZF/R) cells, but markedly enhanced basal ALDO production by dispersed zona glomerulosa (ZG) cells (minim al and maximal effective concentrations were 10(-9) M and 10(-7) M). V ideo-imaging analysis showed that NMK (10(-8) M) increased intracellul ar Ca2+ concentration in dispersed ZG cells, but not in ZF/R ones. The se findings indicate that NMK exerts a complex modulatory action on th e rat HPA axis: low doses of NMK appear to evoke a transient stimulati on of ACTH release, while high doses seem to exert a short-term inhibi tion of glucocorticoid synthesis followed by the compensatory hypersec retion of ACTH; moreover, elevated doses of NMK also exert a strong AL DO secretagogue action by acting directly on the ZG cells.