Tetronothiodin, a novel CCKB receptor ligand, antagonizes cholecystokinin-induced Ca2+ mobilization in a pituitary cell line
| Autor: | Tsutomu Kudoh, Mikio Arisawa, Atsuko Nakano, Hiromi Nagase, Mari Takamiya, Toshikazu Kuwahara, Tatsuo Ohtsuka, Hiroyuki Yoshizaki |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Thiophenes Biology Cholecystokinin receptor Sincalide Cell Line Anterior pituitary Pituitary Gland Anterior Internal medicine medicine Animals Rats Wistar Receptor Furans Cholecystokinin Pharmacology Binding Sites Antagonist Ligand (biochemistry) Receptor antagonist Molecular biology Rats medicine.anatomical_structure Endocrinology Cell culture Autoradiography Calcium Receptors Cholecystokinin hormones hormone substitutes and hormone antagonists |
| Zdroj: | European journal of pharmacology. 221(1) |
| ISSN: | 0014-2999 |
| Popis: | We found a novel nonpeptide CCKB receptor antagonist, tetronothiodin (Ro 09-1468), in the culture broth of Streptomyces sp. NR0489. The structure of the compound (C31O8H38S), which has a 19-membered ring with an alpha-acyltetronic acid and tetrahydrothiophene moiety, is completely different from that of any known CCK receptor antagonist. Tetronothiodin inhibited [125I]CCK-8 binding to rat brain CCKB receptors with an IC50 of 3.6 nM, whereas it showed only weak affinity for rat CCKA receptors (IC50 = 70 microM). As demonstrated autoradiographically, tetronothiodin concentration dependently inhibited [125I]CCK-8 binding to CCKB receptors in rat forebrain slices. The effects of tetronothiodin on cytosolic Ca2+ concentrations in GH3 cells, a rat anterior pituitary tumor cell line, were investigated with the fura-2 method. Tetronothiodin inhibited CCK-8-induced Ca2+ mobilization without affecting basal cytosolic Ca2+ concentrations. In conclusion, tetronothiodin is a new, potent and highly selective CCKB receptor antagonist. It is a useful tool for investigating the pharmacological and physiological roles of CCKB receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|