Characterization of substance P and somatostatin receptors on adrenal chromaffin cells using structural analogues

Substance P (SP) and somatostatin (SRIF) are known to inhibit the nicotine-induced release of catecholamines (CAs) from isolated adrenal chromaffin cells in culture22,24. In order to characterize the receptors mediating this action, we have tested several SP and SRIF analogues for their effects on release of [3H]L-norepinephrine ([3H]NE) from chromaffin cell cultures. SP-free acid and a series of 11 SP analogues, in which each amino acid of SP is replaced in turn by L-alanine, all inhibited the nicotine-induced release of [3H]NE from these cultures. The rank order of potency of the analogues for this action was similar to their reported order of potency in other SP-responsive tissues. The least potent were SP-free acid, [Ala7]-SP, [Ala10]-SP, [Ala8]-SP and [Ala11]-SP, while the potencies of the Ala 1 to 6 analogues and [Ala9]-SP were closer to that of SP. [Leu7]- and [Leu7,8]-SP had potencies similar to that of SP. SP itself had no effect on basal [3H]NE release and only the highest concentrations of some of the analogues tested had an effect (enhancement) on basal [3H]NE release. The results suggest that adrenal chromaffin cells possess a specific SP receptor mediating inhibition of agonist-induced CA release and that the binding site of this receptor shares similar structural requirements with the binding site of the SP receptor on other tissues. Several SRIF analogues, which have been previously shown to be more potent than native SRIF at selective SRIF receptors2,3,31, 35, were compared to SRIF for effects on [3H]NE release from chromaffin cell cultures. These analogues were found to be active but less potent than SRIF in inhibiting nicotine-induced [3H]NE release from these cultures, suggesting that the site mediating this action differs in its structural requirements from the SRIF receptor found in some other tissues.