The possible role of endogenous substance P in the modulation of the response of rat pituitary-adrenal axis to stresses.

The role played by endogenous substance P (SP) in the regulation of hypothalamo-pituitary-adrenal (HPA) axis was investigated in the rat. Normal and ether-stressed (2 min ether-vapor inhalation) or cold-stressed (20 min at 4 degrees C) animals were given a bolus subcutaneous injection of 100 nmol spantide (SPA) a specific antagonist of SP; their blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA, 1, 2 or 4 h after the injection. SPA did not evoke significant changes in the basal plasma levels of the three hormones. Ether and cold stresses markedly raised the blood concentrations of ACTH, ALDO and B, being maximal response observed after 1 or 2 h. SPA notably enhanced the responses of the three hormones to ether stress. SPA magnified ALDO and B responses to cold stress, but it notably depressed ACTH one. In light of these findings, it may be concluded that (i) endogenous SP does not affect basal activity of rat HPA axis, but it exerts an inhibitory action on its response to the stresses, especially the ether-inhalation one: and (ii) different mechanisms are involved in the cold and ether stress-induced activation of the HPA axis.