Abstract

A highly purified preparation of calmodulin activated a calmodulin-deficient phosphodiesterase by more than 10-fold. This activation of phosphodiesterase by calmodulin was completely inhibited by two opioid peptides, beta-endorphin and dynorphin, at concentrations that had no appreciable effect on the basal phosphodiesterase activity. By contrast, similar concentrations of other structurally related peptides, including alpha-endorphin, (des-Tyr1)-gamma-endorphin, Leu-enkephalin, and Met-enkephalin, failed to block calmodulin's activation of phosphodiesterase. The inhibition by beta-endorphin of calmodulin's action was not reversed by calcium or by the opiate antagonist naloxone but was overcome by increasing the concentration of calmodulin. Equilibrium dialysis studies showed that 125I-labeled beta-endorphin bound directly to calmodulin in a saturable, calcium-dependent manner with a dissociation constant of approximately 4.6 microM. There was substantially less binding of beta-endorphin to troponin-C and little or no calcium-dependent binding of beta-endorphin to bovine serum albumin, lactalbumin, or histone. This interaction of beta-endorphin with calmodulin was similar in several respects to the interaction of certain antipsychotic drugs to calmodulin and may explain certain of the peptide's biochemical effects.