Administered peptides inhibit the degradation of endogenous peptides. The dilemma of distinguishing direct from indirect effects

Frank S. LaBella, Jonathan D. Geiger, Gary B. Glavin

Research output: Contribution to journalArticle

38 Scopus citations


Virtually all peptides are biologically active following central administration as a consequence of both direct and indirect cellular actions. Direct effects are mainly interactions with specific membrane receptors but may include unions with other components of the receptor/effector complex. Significant indirect biological effects of exogenous peptides, including apparent secretagogue effects on endogenous peptides largely overlooked in practice, result from extensive competition with endogenous peptides for degradative enzymes (peptidases). A consequence of this competition is enhancement of tonic or intermittent activity of endogenous peptides. The pharmacological profile of any peptide reflects or includes, therefore, the spectrum of endogenous peptides that is protected from peptidase action. It is likely that certain pharmacologically active peptides, including a large number of di-, tri- and oligo-peptides, elicit responses mainly or exclusively by competing for peptidases. Therefore, reliable estimates of the relative contributions of direct and indirect actions of exogenous peptides may be difficult, if not impossible, to obtain.

Original languageEnglish (US)
Pages (from-to)645-660
Number of pages16
Issue number4
Publication statusPublished - Jan 1 1985



  • Oligopeptides
  • Peptidase
  • Peptidase inhibition
  • Peptides
  • Release

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Cite this