Theophylline inhibits transcellular Ca transport in intestine and Ca binding by CaBP.
Theophylline, when added to the incubation medium of everted duodenal sacs prepared from rats on a low-calcium diet, was found to inhibit transcellular Ca transport in a concentration-dependent manner, with an inhibitor constant (Ki) of 10.8 mM theophylline. Neither the rate of cellular Ca entry, as evaluated with the aid of brush-border membrane vesicles, nor the rate of cellular Ca extrusion, assessed by measuring ATP-dependent Ca uptake of basolateral membrane vesicles, was significantly altered by the addition of theophylline to the uptake media. However, Ca-binding by calcium-binding protein (CaBP; calbindin D9k), Mr approximately 8,800) was depressed by theophylline in a concentration-dependent manner, with Ki = 3.2 mM theophylline. Theophylline had no effect on Ca binding by calmodulin and the theophylline-induced inhibition of transcellular calcium transport was independent of adenosine 3',5'-cyclic monophosphate levels. Theophylline also had no effect on paracellular Ca movement. Since the theophylline-induced inhibition of Ca-binding by CaBP paralleled the inhibition of transcellular Ca transport, it is concluded that CaBP functions in transcellular Ca transport via its ability to bind Ca.
Pansu
D
D
Ecole Pratique des Hautes Etudes, Hôpital E. Herriot, Lyon, France.
Bellaton
C
C
Roche
C
C
Bronner
F
F
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D009130:Muscle, Smooth / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology*
D002147:Calmodulin; D064030:S100 Calcium Binding Protein G; D005576:Colforsin; D013806:Theophylline; D002118:Calcium