Is [3H]-tiotidine a specific ligand for the H2-receptor?
The H2-antagonist tiotidine inhibited the H2-receptor-mediated, histamine-induced increase in cyclic AMP in dispersed mucosal cells from guinea pig stomach (Ki, 4 X 10(-8) M). The radiolabeled [3H]-tiotidine bound specifically and reversibly to the same cells with a half-maximal binding occurring at 5 X 10(-7) M tiotidine. The dissociation of bound [3H]-tiotidine from gastric cells and the Scatchard analysis of the binding binding data suggest the existence of additional binding sites for tiotidine. Eight other antagonists which inhibited the H2-receptor-mediated increase in cyclic AMP also inhibited [3H]-tiotidine binding. However, the potencies of these agents for binding did not agree with their effects on cyclic AMP. The selective H2-agonists impromidine and dimaprit which increased cyclic AMP caused only partial inhibition of [3H]-tiotidine binding. These results demonstrate that [3H]-tiotidine has limited binding to the H2-receptors and as such [3H]-tiotidine is not a suitable ligand for labelling the H2-receptor on gastric mucosal cells.
Batzri
S
S
Harmon
J W
JW
D000818:Animals; D001667:Binding, Competitive; D002927:Cimetidine / Q000031:analogs & derivatives* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D011968:Receptors, Histamine / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000378:metabolism*
D006635:Histamine H2 Antagonists; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D000242:Cyclic AMP; C023990:tiotidine