KCl (40 mM) caused reproducible relaxations in frog esophagus. N-G-nitro-L-arginine (L-NOARG; 1-100 mu M), a steriospecific inhibitor of nitric oxide synthase (NOS), completely inhibited the relaxations induced by KCl but not those induced by vasoactive intestinal polypeptide (VIP) antagonist. The inhibitory effect of L-NOARG was prevented by L-arginine (L-ARG; 0.1-1 mM), the precursor of nitric oxide (NO) biosynthesis, but not by D-arginine (D-ARG; 0.1-0.5 mM), the enantiomer of L-arginine. L-ARG or D-ARG alone did not significantly modify the effect of KCl. The relaxations to KCl were significantly inhibited by omega conotoxin (omega-conotoxin; 0:1 mu M), a selective blocker of N-type calcium channels. Propranolol (0.1-1 mu M), a nonselective blocker of P-adrenergic receptors, prazosine (0.01-0.1 mu M), a selective blocker of alpha(1)-actrenergic receptors, phentolamine (0.1-1 mu M), a nonselective blocker of adrenergic receptors, atropine, a selective blocker of muscarinic cholinergic receptors, and lidocaine (1-10 mu M), a blocker of sodium channels, had no effect on KCl-evoked relaxations. Caffeine (500 mu M),an intracellular calcium releasing agent, did not significantly modify the effect of KCl. In contrast, ruthenium red (100 mu M), a selective blocker of ryanodine receptors (intracellular Ca2+ channels), significantly inhibited these relaxations. Similarly, potassium channel blockers such as 4-aminopyridine (4-AP; 100 mu M) and tetraethylammonium (TEA; 100 mu M) caused a significant inhibition on relaxations to KCl. In addition, ouabain (100 mu M), a specific blocker of Na+-K+-ATPase, also caused a significant inhibition on these relaxations. The results suggest that NO, Na+-K+-ATPase and potassium channels may have a role on relaxations induced by 40 mM KCl in the frog esophagus. (C) 2009 Elsevier BY. All rights reserved.