Inhibitory effect of etintidine (BL-5641), a new type of H2 receptor antagonist, on binding of [3H]-cimetidine to plasma membrane and histamine-stimulated cellular cAMP production in isolated guinea pig gastric glands.
A comparative study was carried out between the inhibitory effects of cimetidine and those of etintidine (BL-5641), a new type of H2 receptor antagonist, on the binding of [3H]-cimetidine to plasma membranes as well as on histamine-stimulated cellular cAMP production in isolated guinea pig gastric glands. Both cimetidine and etintidine inhibited the binding of [3H]-cimetidine to plasma membranes, in a dose-dependent manner, with an IC50 of 1.70 X 10(-6) M and 0.51 X 10(-6) M, respectively. The two drugs also inhibited histamine-stimulated cellular cAMP production in a dose-dependent manner, shifting the histamine dose-dependent curve of cellular cAMP production to the right. The PA2 calculated from the result obtained was 6.41 for cimetidine and 6.82 for etintidine. These results indicate that etintidine is an H2 receptor antagonist at the cellular level and that its inhibitory effect is approximately 2.5 times as potent as that of cimetidine.
Nishihara
S
S
Tanaka
A
A
Tazoe
A
A
Yoshida
K
K
Misawa
T
T
Ibayashi
H
H
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002927:Cimetidine / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000378:metabolism*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism*; D066298:In Vitro Techniques; D011968:Receptors, Histamine / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006635:Histamine H2 Antagonists; D007093:Imidazoles; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; C036616:etintidine; D000242:Cyclic AMP