Effect of substance P (SP) and the N-terminal SP-analogue SP (1-4) on the pre- and postsynaptic transmitter release in rat adrenal gland slices.

In the adrenal medulla ACh released from endings of splanchnic nerve stimulates catecholamine secretion by activation of nicotinic receptors localized on the chromaffin cells. Neuropeptides including SP may influence the catecholamine secretion. This report represents a study of the nature of the effect of SP and SP (1-4) on the cholinergic-adrenergic interaction in rat adrenal gland slices. In particular, the contributions of pre- and postsynaptic effects have been examined. The effect of SP and SP (1-4) on the electrically stimulated 3H-ACh outflow and on the nicotine-evoked 3H-noradrenaline (NA) outflow was determined. SP and SP (1-4) inhibited the evoked 3H-NA outflow in a dose-dependent manner. A dose-dependent inhibition by SP and SP (1-4) was also found in respect to the stimulated 3H-ACh outflow. Both substances had no effect on the basal 3H-transmitter outflow. SP had a stronger inhibitory effect on 3H-ACh outflow (ID50 = 1 X 10(-7) M) than on evoked 3H-NA outflow (ID50 = 8 X 10(-7) M). We discuss the functional role of SP to modulate the catecholamine secretion in adrenals especially in stressful situations as well as consequences with regard to the synthesis of selectively acting SP-analogues.