Effects of calcium antagonist TMB-8 on active Na and Cl transport in rabbit ileum

The effects of 3,4,5-trimethoxybenzoate 8-(N,N-diethylamino)octyl ester (TMB-8), an agent that traps calcium within intracellular stores, were studied on active electrolyte transport in rabbit ileum under basal conditions and after altering transport by increasing the intracellular cAMP content or by exposure to two agonists that act by altering intracellular Ca²⁺ (carbachol and setotonin). TMB-8 decreased the ileal short-circuit current and increased active Na and Cl absorption by increasing the mucosal-to-serosal Na and Cl fluxes. These effects were reversed by increasing the bathing solution Ca²⁺ to 4 mM, a concentration that itself did not alter basal ileal transport. The maximum glucose- and amino acid (alanine)-induced increase in Na absorption in the ileum was not affected by TMB-8. The effects on basal transport of TMB-8 were not associated with a change in ⁴⁵Ca²⁺ entry across the ileal serosal surface. TMB-8 did not alter cAMP-induced secretion, as judged by its lack of effect on the increase in short-circuit current caused by 8-bromo-cAMP (10^-4 M). TMB-8 totally prevented the transport effects of carbachol but did not inhibit the effects of serotonin. These data suggest a role for intracellular Ca²⁺ in regulation of basal ileal Na and Cl transport but not in cAMP-induced secretion. There appear to be several pools of intracellular Ca²⁺ involved in neurohumoral effects on active electrolyte transport.