Binding of [3H]ICIA 5165, an H2-receptor antagonist to guinea pig gastric mucosa.

ICIA 5165, 2-guanidino-4-[4-(2-cyano-3-methylguanidino)butyl] thiazole, a selective histamine H2-receptor antagonist was radiolabelled with tritium to a specific activity of 50.8 Ci/mmol for use in binding studies. Radiolabelling did not impair bioactivity. Binding characteristics of [3H]ICIA 5165 to guinea pig gastric mucosa were determined. Ligand binding was rapid, reaching equilibrium within five minutes at 0 degrees C, reversible and saturable. Specific [3H]ICIA 5165 binding had an equilibrium dissociation constant of 1.29 X 10(-8) M, determined by Scatchard plot analysis, and of 1.02 X 10(-8) M, calculated from the ratio of the dissociation to association rate constants. A Hill number, nH, of 1.02 was determined for the specific binding component. Specific binding of [3H]ICIA 5165 to gastric mucosal supernatant was not inhibited by methapyrilene, diphenhydramine, mepyramine, d-chlorpheniramine or l-chlorpheniramine (all at 10(-7) M), or by atropine or propranolol (both at 10(-6) M). Specific [3H]ICIA 5165 binding was inhibited in a concentration dependent manner by non-radioactive ICIA 5165 and tiotidine, as well as by a variety of other agents, with H2 agonist or H2 antagonist properties. In competition experiments, however, difficulties encountered in accurately defining the degree of specific binding indicate some reservation should be observed in interpreting these results.