The Role of histidine-1 in Glucagon Action

Arch Biochem Biophys. 1993 Feb 1;300(2):747-50. doi: 10.1006/abbi.1993.1103.


The identification of position 9 aspartic acid in glucagon as a critical residue for transduction reinforced the notion that specific residues in the peptide sequence dictate either receptor recognition or biological activity. It was evident from our studies that Asp9 operates in conjunction with His1 as part of the activation mechanism that follows binding to the glucagon receptor. This investigation was conducted to delineate structural features of histidine that contribute to its role in glucagon action. We report, based on binding and activity data from 10 replacement analogs, that the imidazole ring of His1 furnishes an aromatic determinant for receptor binding affinity and that its protonatable imidazole nitrogen is important for transduction.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • Cell Membrane
  • Cyclic AMP / metabolism
  • Glucagon / analogs & derivatives
  • Glucagon / chemistry
  • Glucagon / metabolism*
  • Glucagon / pharmacology*
  • Histidine* / analogs & derivatives*
  • Liver / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Gastrointestinal Hormone / metabolism*
  • Receptors, Glucagon
  • Structure-Activity Relationship


  • Receptors, Gastrointestinal Hormone
  • Receptors, Glucagon
  • Histidine
  • Glucagon
  • Cyclic AMP
  • Adenylyl Cyclases