Biomaterial Database

Inhibition of bone resorption by H+/K(+)-ATPase inhibitors. 1993

R Sarges, and A Gallagher, and T J Chambers, and L A Yeh

Pfizer Central Research, Pfizer Inc., Groton, Connecticut 06340.

We have found that 3-(3-(ethoxycarbonyl)propionyl)-8-methoxy-4-((2- methylphenyl)amino)quinoline (1, CP-113,411), a reversible inhibitor of gastric H+/K(+)-ATPase (IC50 10-20 mM), is also a potent inhibitor of bone resorption by osteoclasts in a bone slice assay at concentrations as low as 10(-7) M, with an IC50 of 2 mM. By contrast, the structurally related H+/K(+)-ATPase inhibitor 2 (3-(ethoxycarbonyl)-8-methoxy-4-((2-methylphenyl)amino)quinoline) disclosed by Robins is slightly more potent as an inhibitor of the gastric enzyme (IC50 3-10 microM in our hands) but less efficacious than 1 as an inhibitor of osteoclasts in the bone slice assay at the lower concentrations (no effect at < or = 10(-6) M, IC50 4 mM). These findings suggest that osteoclasts contain an H+/K(+)-ATPase-like enzyme which differs from the gastric one.

UI	MeSH Term	Description	Entries
D010010	Osteoclasts	A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.	Odontoclasts,Cementoclast,Cementoclasts,Odontoclast,Osteoclast
D001862	Bone Resorption	Bone loss due to osteoclastic activity.	Bone Loss, Osteoclastic,Osteoclastic Bone Loss,Bone Losses, Osteoclastic,Bone Resorptions,Loss, Osteoclastic Bone,Losses, Osteoclastic Bone,Osteoclastic Bone Losses,Resorption, Bone,Resorptions, Bone
D005753	Gastric Mucosa	Lining of the STOMACH, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. The surface cells produce MUCUS that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the LAMINA PROPRIA at various region of the stomach (CARDIA; GASTRIC FUNDUS; and PYLORUS), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, HYDROCHLORIC ACID, or hormones.	Cardiac Glands,Gastric Glands,Pyloric Glands,Cardiac Gland,Gastric Gland,Gastric Mucosas,Gland, Cardiac,Gland, Gastric,Gland, Pyloric,Glands, Cardiac,Glands, Gastric,Glands, Pyloric,Mucosa, Gastric,Mucosas, Gastric,Pyloric Gland
D000634	Aminoquinolines	Quinolines substituted in any position by one or more amino groups.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000897	Anti-Ulcer Agents	Various agents with different action mechanisms used to treat or ameliorate PEPTIC ULCER or irritation of the gastrointestinal tract. This has included ANTIBIOTICS to treat HELICOBACTER INFECTIONS; HISTAMINE H2 ANTAGONISTS to reduce GASTRIC ACID secretion; and ANTACIDS for symptomatic relief.	Anti-Ulcer Drugs,Agents, Anti-Ulcer,Anti Ulcer Agents,Anti Ulcer Drugs,Drugs, Anti-Ulcer
D013386	Succinates	Derivatives of SUCCINIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a 1,4-carboxy terminated aliphatic structure.	Succinic Acids,Acids, Succinic
D013552	Swine	Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).	Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D017506	H(+)-K(+)-Exchanging ATPase	An enzyme isolated from the GASTRIC MUCOSA that catalyzes the hydrolysis of ATP coupled with the exchange of hydrogen and potassium ions across the cell wall. This enzyme was formerly listed as EC 3.6.1.36.	ATPase, Hydrogen, Potassium,Adenosinetriphosphatase, Hydrogen, Potassium,H(+)-K(+)-Transporting ATPase,Hydrogen, Potassium ATPase,Hydrogen, Potassium, Adenosinetriphosphatase,Adenosine Triphosphatase, Hydrogen, Potassium,Gastric H(+) K(+) ATPase,Hydrogen, Potassium, Adenosine Triphosphatase,Hydrogen-Potassium-Exchanging ATPase,Potassium Hydrogen ATPase,ATPase Hydrogen, Potassium,ATPase, Hydrogen-Potassium-Exchanging,ATPase, Potassium Hydrogen,Hydrogen Potassium Exchanging ATPase
D054328	Proton Pump Inhibitors	Compounds that inhibit H(+)-K(+)-EXCHANGING ATPASE. They are used as ANTI-ULCER AGENTS and sometimes in place of HISTAMINE H2 ANTAGONISTS for GASTROESOPHAGEAL REFLUX.	Proton Pump Inhibitor,Inhibitor, Proton Pump,Inhibitors, Proton Pump,Pump Inhibitor, Proton