Studies on role of calmodulin in Ca2+ regulation of rabbit ileal Na and Cl transport.
To study the role of calmodulin in regulation of rabbit ileal active electrolyte transport by Ca2+, the effects of the Ca2+-calmodulin antagonist naphthalenesulfonamides W12 and W13 and the weak Ca2+-calmodulin antagonist promethazine, a phenothiazine, were studied on basal ileal Na and Cl transport and on secretion stimulated by Ca2+ and by cAMP. The naphthalenesulfonamides and promethazine all stimulated basal ileal Na and Cl absorption. The stimulation of Na absorption was dependent on Cl in the bathing solutions, and the stimulation of Cl absorption was Na dependent. This suggests that the transport process stimulated was the neutral, linked NaCl absorptive process. W13, which is a better Ca2+-calmodulin antagonist but has similar hydrophobic properties to W12, stimulated active ileal absorption at a lower concentration than W12, suggesting that the naphthalenesulfonamide-induced stimulation of active ileal absorption was not due to the hydrophobic properties of these drugs but could be due to their effects on the calcium-binding protein calmodulin. W12, W13, and promethazine did not alter paracellular transport, not affecting dilution potentials or structural features of the paracellular pathway. W12 and W13 did not decrease the changes in active ileal Na and Cl transport caused by increasing ileal cAMP content or intracellular Ca2+. This suggests that calmodulin is not directly involved in the active electrolyte secretion caused by increased intestinal Ca2+ or cAMP.
M
M
Donowitz
J
J
Wicks
J L
JL
Madara
G W
GW
Sharp
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D011398:Promethazine / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D013268:Stimulation, Chemical; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D002712:Chlorides; D007473:Ion Channels; D013449:Sulfonamides; D014268:Trifluoperazine; C040184:W 12; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D012964:Sodium; D000242:Cyclic AMP; D011398:Promethazine; D002118:Calcium