Receptor Regulatory Properties Evident in the Molecular Similarity of Histamine and Purine Nucleotides

Abstract

The relative configurations of some low-molecular-weight hormones and guanosine triphosphate are similar. Because adenosine and guanosine nucleotides, in cyclic and non-cyclic forms, participate in hormone receptor activation mechanisms, this investigation of molecular similarity has been extended to both purine nucleotides and ligands operating at histamine receptor sub-types. Nitrogen atoms in mono-cation minimum energy conformers of histamine and H1 agonists relate to a specific pattern of nitrogen atoms in the guanine ring. Nitrogen atoms in uncharged minimum energy conformers of histamine H2 and H3 agonists relate to a different pattern of nitrogen atoms in the adenine ring. Minimum energy conformers of H1, H2 and H3 antagonists fit to specific nitrogen atoms in the same purine ring system as their corresponding agonist. Structural similarity, relevant to H1 receptor activation, is also evident in histamine and arginine molecules. Histamine receptor design may be based on purine nucleotide structure. Histamine H1 receptors demonstrate complementarity for the guanine ring. Histamine H2 and H3 receptors show complementarity for the adenine ring system.