Molecular basis for the interaction of histamine with the histamine H2 receptor.

Tiotidine binding, the generation of cAMP in response to histamine was maintained

I Gantz; J DelValle; L.D. Wang; T Tashiro; G Munzert; Y.J. Guo; Y Konda; T Yamada


Scholarcy highlights

  • Tiotidine binding, the generation of cAMP in response to histamine was maintained
  • Consistent with the binding datawas the observation that histamine had no effect on cAMP generation in Hepa cells that expressed the Aspg8mutation
  • As shown in Fig. 1mutations of the aspartic observed with the Ala186and Ala'm-Ala'go mutant receptors acid residue at the 98 or 186 position resulted in complete was only partially reversed with cimetidine
  • Incontrast, a single mutation of the Thrlgo Atola'" or Cyslg0resulted ina receptor that was capable of binding [rneth~l-~HItiotidine, but waith lower efficacy despite the fact that the Hepcaells expressing The analogy between histamine and catecholamine recepthe AlaIg0or CYS'~Omutations had an equivalent or greater tors extends beyond the observations that led to the develnumber of receptors by Scatchardanalysis than opment of selective HZ receptor antagonists.Both receptor families belongto the broad claosfsseven transmembrane G
  • The EC, for definesthe H2selectivity of the receptor, and an additional this response was unchanged from that observed with the amino acid residue in the fifth transmembrane domain wild-type H2 receptor
  • It is of note that theamino acids that correspond to consistent with the observations by Weinstein et al that the Aspgs, Asp1", and Thrlgoresidues of the canine H2 histaon the N(3)tHautomer of histamine will bind to H2 receptors. mine receptor are conserved in the structure of the human

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