High affinity 3H-cimetidine binding in guinea-pig tissues

[3H]‐idazoxan binds with high affinity to two sites on hamster adipocytes: an α2‐adrenoceptor and a non‐adrenoceptor site

“…(Meeley et al, 1986;Ernsberger et al, 1987). This second site has also been identified in human brainstem (Bricca et al, 1988) where it is labelled by [3H]-clonidine (Bricca et al, 1989 (Rising et al, 1980;Subramanian & Slotkin, 1981). Clonidine and phentolamine potently inhibited [3H]-cimetidine binding to the imidazole site in rat brain (Burkard, 1978;Subramanian & Slotkin, 1981).…”

Specific 3H-Cimetidine Binding to Receptors in the Submandibular Gland of the Rat

“…It is also of interest to note that the displacement of 3H cimetidine by H2-receptor agonists occurs in the micromolar range irrespective of whether these agonists are imidazole or non-imidazole derivatives. This observation is also seen in the results of others (4,5) and those of Gajtkowski and co-workers who have shown specific H2-receptor ligand binding in the guinea pig cerebral cortex with 3H-tiotidine, but was not able to obtain the same results using the brain of a different animal or the right atrium and gastric mucosae of the same animal (11). …”

“…Two other considerations also prompted us to investigate the H2-receptors of the salivary gland. First, 3H-cimetidine and other tritiated imidazole ligands had been shown to bind to an imidazole recognition site rather than the pharmacological H2 receptor in tissues which have been shown by classical pharmacological experiments to possess H2-receptors (4,5). The status of the imidazole recognition site vis-a-vis the H2 receptor in the salivary gland is currently unknown.…”

The binding of [3H]‐tiotidine to homogenates of guinea‐pig lung parenchyma

“…For each H2-compound, the first phase -3 displacement was studied in detail as this was taken to represent displacement of [3H]-tiotidine from the H2-receptor, occurring over the pharmacologically active concentration range of each competing H2-compound (Black et al, 1972;Black et al, 1973;Brimblecombe et al, 1975;Yellin et al, 1979;Bradshaw et al, 1979;Gajtkowski et al, 1983). Figure 6 shows the first phase displacement of bound [3H]-tiotidine by histamine, burimamide and YMI 1 170, a selective antagonist at histamine H2-receptors (Takeda et al, 1982 (Gajtkowski et al, 1983 (Burkard, 1978;Kendall et al, 1980), where it was later realized that (3H]-cimetidine was in fact labelling an imidazole recognition site which was completely unrelated to the pharmacological receptor (Rising et al, 1980;Smith et al, 1980). In displacement experiments it is very important to include compounds of the same pharmacological class but with substantial variation of chemical structure to establish that the ligand is labelling a specific pharmacological receptor.…”

“…More recently, results from work with [3H]-cimetidine have suggested a high affinity binding site for this ligand which is unrelated to the pharmacological receptor, but which recognizes the imidazole moiety of this compound (Rising et al, 1980;Smith et al, 1980). [3H]-tiotidine is a more potent H2-antagonist than either ranitidine or cimetidine (Yellin et al, 1979) and has recently been shown to meet the criteria for labelling the H2-receptor in membranes from the guinea-pig cerebral cortex (Gajtkowski et al, 1983).…”