Molecular mechanism of KCl-induced relaxation of the esophagus.
KCl (40 mM) caused reproducible relaxations in frog esophagus. N(G)-nitro-L-arginine (L-NOARG; 1-100 microM), 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 microM), a selective blocker of N-type calcium channels. Propranolol (0.1-1 microM), a nonselective blocker of beta-adrenergic receptors, prazosine (0.01-0.1 microM), a selective blocker of alpha(1)-adrenergic receptors, phentolamine (0.1-1 microM), a nonselective blocker of adrenergic receptors, atropine, a selective blocker of muscarinic cholinergic receptors, and lidocaine (1-10 microM), a blocker of sodium channels, had no effect on KCl-evoked relaxations. Caffeine (500 microM), an intracellular calcium releasing agent, did not significantly modify the effect of KCl. In contrast, ruthenium red (100 microM), a selective blocker of ryanodine receptors (intracellular Ca(2+) channels), significantly inhibited these relaxations. Similarly, potassium channel blockers such as 4-aminopyridine (4-AP; 100 microM) and tetraethylammonium (TEA; 100 microM) caused a significant inhibition on relaxations to KCl. In addition, ouabain (100 microM), 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.
Yaktubay Döndaş
Naciye
N
Department of Pharmacology, Medical Faculty, Cukurova University, Adana, Turkey. yakdas25@cu.edu.tr
Karataş
Yusuf
Y
Kaya
Derya
D
Soylu
Neslihan
N
Singirik
Ergin
E
Baysal
Firuz
F
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology*; D011894:Rana pipiens; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D019335:Nitroarginine; D009569:Nitric Oxide; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase