Tags

Type your tag names separated by a space and hit enter

Effects of H2-receptor antagonists on 3H-cimetidine binding and histamine-stimulation of cellular cAMP in isolated guinea pig gastric glands.
Jpn J Pharmacol. 1987 Sep; 45(1):97-105.JJ

Abstract

3H-Cimetidine binding to plasma membranes of isolated guinea pig gastric glands was investigated, and the effects of five H2-receptor antagonists on 3H-cimetidine binding and histamine stimulation of cellular cAMP were compared. Of the five cations tested, Cu++ markedly increased specific 3H-cimetidine binding. 3H-Cimetidine had high affinity (Kd = 0.41 x 10(-6) M) and low affinity (Kd = 12.8 x 10(-6) M) binding sites. Cimetidine and etintidine were potent inhibitors of 3H-cimetidine binding, while famotidine, ranitidine and TZU-0460 were not. Histamine stimulation of cellular cAMP was competitively inhibited by H2-receptor antagonists yielding pA2 values of 6.41 for cimetidine, 6.82 for etintidine, 6.87 for ranitidine, 6.94 for TZU-0460 and 7.60 for famotidine. Because the KB value (log KB = -pA2) of 0.39 x 10(-6) M for cimetidine is close to the Kd value for the high affinity 3H-cimetidine binding site, it is presumed to represent a part of the H2-receptor, and the relative potency of etintidine against cimetidine in inhibiting 3H-cimetidine binding is similar to that in inhibiting histamine stimulation of cellular cAMP. These results suggest that imidazole-derived H2-receptor antagonists (cimetidine and etintidine) and non-imidazole H2-receptor antagonists (famotidine, ranitidine and TZU-0460) compete with histamine at different sites on the H2-receptor of the gastric glands.

Authors+Show Affiliations

Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

2890783

Citation

Tanaka, A, et al. "Effects of H2-receptor Antagonists On 3H-cimetidine Binding and Histamine-stimulation of Cellular cAMP in Isolated Guinea Pig Gastric Glands." Japanese Journal of Pharmacology, vol. 45, no. 1, 1987, pp. 97-105.
Tanaka A, Nishihara S, Misawa T, et al. Effects of H2-receptor antagonists on 3H-cimetidine binding and histamine-stimulation of cellular cAMP in isolated guinea pig gastric glands. Jpn J Pharmacol. 1987;45(1):97-105.
Tanaka, A., Nishihara, S., Misawa, T., & Ibayashi, H. (1987). Effects of H2-receptor antagonists on 3H-cimetidine binding and histamine-stimulation of cellular cAMP in isolated guinea pig gastric glands. Japanese Journal of Pharmacology, 45(1), 97-105.
Tanaka A, et al. Effects of H2-receptor Antagonists On 3H-cimetidine Binding and Histamine-stimulation of Cellular cAMP in Isolated Guinea Pig Gastric Glands. Jpn J Pharmacol. 1987;45(1):97-105. PubMed PMID: 2890783.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of H2-receptor antagonists on 3H-cimetidine binding and histamine-stimulation of cellular cAMP in isolated guinea pig gastric glands. AU - Tanaka,A, AU - Nishihara,S, AU - Misawa,T, AU - Ibayashi,H, PY - 1987/9/1/pubmed PY - 1987/9/1/medline PY - 1987/9/1/entrez SP - 97 EP - 105 JF - Japanese journal of pharmacology JO - Jpn. J. Pharmacol. VL - 45 IS - 1 N2 - 3H-Cimetidine binding to plasma membranes of isolated guinea pig gastric glands was investigated, and the effects of five H2-receptor antagonists on 3H-cimetidine binding and histamine stimulation of cellular cAMP were compared. Of the five cations tested, Cu++ markedly increased specific 3H-cimetidine binding. 3H-Cimetidine had high affinity (Kd = 0.41 x 10(-6) M) and low affinity (Kd = 12.8 x 10(-6) M) binding sites. Cimetidine and etintidine were potent inhibitors of 3H-cimetidine binding, while famotidine, ranitidine and TZU-0460 were not. Histamine stimulation of cellular cAMP was competitively inhibited by H2-receptor antagonists yielding pA2 values of 6.41 for cimetidine, 6.82 for etintidine, 6.87 for ranitidine, 6.94 for TZU-0460 and 7.60 for famotidine. Because the KB value (log KB = -pA2) of 0.39 x 10(-6) M for cimetidine is close to the Kd value for the high affinity 3H-cimetidine binding site, it is presumed to represent a part of the H2-receptor, and the relative potency of etintidine against cimetidine in inhibiting 3H-cimetidine binding is similar to that in inhibiting histamine stimulation of cellular cAMP. These results suggest that imidazole-derived H2-receptor antagonists (cimetidine and etintidine) and non-imidazole H2-receptor antagonists (famotidine, ranitidine and TZU-0460) compete with histamine at different sites on the H2-receptor of the gastric glands. SN - 0021-5198 UR - https://www.unboundmedicine.com/medline/citation/2890783/Effects_of_H2_receptor_antagonists_on_3H_cimetidine_binding_and_histamine_stimulation_of_cellular_cAMP_in_isolated_guinea_pig_gastric_glands_ L2 - https://joi.jlc.jst.go.jp/JST.Journalarchive/jphs1951/45.97?from=PubMed DB - PRIME DP - Unbound Medicine ER -