Ca2+ channel blockers stimulate ileal and colonic water absorption.
The effects of calcium channel blockers on water transport in the rat ileum and distal colon were studied in vivo using the single-pass perfusion technique. Parenteral but not intraluminal verapamil, and parenteral nifedipine increased ileal water absorption, with effects lasting at least 60 min. In contrast, i.p. verapamil had no effect on rat distal colonic water absorption, whereas intraluminal verapamil significantly stimulated colonic water absorption. Similarly, perfusing the rat descending colon with low-Ca2+ Ringer's-HCO3 stimulated colonic water absorption. Verapamil was not antisecretory because the theophylline-induced decrease in ileal water transport was similar in control animals and in animals pretreated with i.p. verapamil. In addition, nifedipine stimulated active Na and Cl absorption in rabbit ileum. These studies demonstrate that the Ca2+ channel blockers verapamil and nifedipine stimulate basal absorption of water in rat ileum and distal colon in vivo, and stimulate active Na and Cl absorption in rabbit ileum in vitro. The verapamil stimulation of colonic water absorption from the luminal surface was duplicated by perfusion with a low-Ca2+ bathing solution. This suggests the presence of apical membrane Ca2+ channels in rat colon, which appear to be involved in regulation of basal water transport, and that these Ca2+ channels are in a partially open state under basal conditions. Because verapamil stimulates absorption systemically (ileum) as well as intraluminally (colon), Ca2+ channel blockers have properties that might be useful in treatment of diarrheal diseases.
Donowitz
M
M
Levin
S
S
Powers
G
G
Elta
G
G
Cohen
P
P
Cheng
H
H
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001834:Body Water / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002712:Chlorides; D001285:Atropine; D002217:Carbachol; D012964:Sodium; D013806:Theophylline; D014700:Verapamil; D000242:Cyclic AMP; D009543:Nifedipine; D002118:Calcium