Synthetic Peptide TPLVTLFK, a Selective Agonist of Nonopioid β-Endorphin Receptor, Reduces the Corticotropin and Corticosterone Response

Abstract

The synthetic peptide octarphin (TPLVTLFK) corresponding to the sequence 12–19 of β-endorphin, a selective agonist of nonopioid β-endorphin receptor, was labeled with tritium to specific activity of 29 Ci/mmol. The analysis of the specific binding of [3H]octarphin to anterior pituitary membranes obtained from rats before and after the lipopolysaccharide (LPS)-injection showed that 2 h after LPS administration the value of maximal binding capacity of the membranes (Bmax) was increased by 1.6 times (Bmax 12.3 ± 0.8 and 20.0 ± 1.9 pmol/mg of protein, respectively), while the binding affinity was not changed (K d 5.8 ± 0.3 and 5.5 ± 0.4 nM, respectively). At the same time, LPS did not have a significant effect on the characteristics of the labeled peptide binding to adrenal cortex membranes. Intranasal injection of octarphin at doses of 10–30 μg/rat was found to reduce the LPS-induced corticotropin and corticosterone response. The effect of the peptide was dose-dependent with a maximum at a dose 20 μg/rat. Aminoguanidine (AG 100 mg/kg i.p.), a selective inducible nitric oxide synthase (iNOS) inhibitor, completely abolished the inhibitory effect of the peptide on the LPS-induced corticotropin and corticosterone response. At the same time, octarphin in vitro stimulated in a time- and concentration-dependent manner the anterior pituitary iNOS expression of rats injected with LPS (1 mg/kg i.p.). The maximum level of the iNOS expression was observed at a peptide concentration of 10 nM after 2 h cultivation. These results indicate that the inhibitory effect of octarphin on LPS-induced secretion of corticotropin and corticosterone due to the ability of the peptide to stimulate the expression of iNOS in the anterior pituitary.