When rat adrenal glands are denervated, large increases in the amounts of enkephalin and enkephalincontaining polypeptides appear. In the normal gland, only trace amounts occur. One of the larger polypeptides (approximately 22,000 daltons) increases rapidly and by 48 hr following denervation, attains 20 times its original level. At this time, the levels of free enkephalins are essentially unchanged. By 96 hr, the 22,000-dalton polypeptide begins to decrease as free enkephalins and intermediate-sized enkephalincontaining polypeptides increase. This series of events is consistent with a precursor (22,000-dalton polypeptide)/product (enkephalin) relationship.

No abstract

The conformations of three adrenal medullary enkephalin containing polypeptides (ECPs) were investigated to gain an understanding of their potential structure-activity relationships. Secondary structure characteristics of peptides E, B, and F were examined by circular dichrosim (CD) under conditions designed to mimic both the soluble state and the anisotropic environment which exists at the biological effector site. Conformational differences between the three peptides were further examined by Fourier Transform Infrared Spectroscopy (FTIR) and by empirical predictions for conformation and hydrophobic periodicity. Although all three peptides have a similar structure, existing in random configurations in aqueous solutions, they do exhibit unique individual potentials to assume secondary structure in less polar environments. These conformational differences may be important factors in determining their unique individual biological activities.

Highly conserved enkephalin containing peptides (ECPs) are selectively processed from proenkephalin, which is synthesized in both the neuroendocrine and immune systems. The reported regulatory effects within the central nervous system and the biologic release patterns from both activated lymphocytes and stimulated adrenal chromaffin cells suggest the ECPs may act as regulatory factors of the immune system. We tested the effects of three of the ECPs, Peptides F, E, and B, on the in vitro Ab-forming cell (AFC) response murine splenocytes to antigenic challenge. In contrast to the immunosuppressive effects of the pentapeptide enkephalins, physiologic concentrations of the ECPs significantly enhanced the AFC response to both T cell-dependent and T cell-independent Ags. The effects are not sensitive to competition by the opiate receptor antagonist, naloxone, suggesting cell surface interactions that do not involve classical opiate receptors. These studies provide evidence that the effects are mediated through T cells rather than B cells. Peptide F-treated splenocytes also showed a significant enhancement of the AFC response to suboptimal Ag concentrations, suggesting a mechanism of action in which the ECPs may act to lower the threshold of activation of the effector cell. These results suggest that the ECPs are physiologically important modifiers of the humoral immune response. Given their release patterns and demonstrated action on the in vitro immune response, the proenkephalin-derived ECPs have the potential to be involved in both paracrine and autocrine regulatory networks within the immune system and as a positive immunoregulatory effect from the neuroendocrine system.