The effect of cadmium on the responses of isolated mouse esophageal striated muscle to carbachol

ABSTRACT The Effect of Cadmium on The Responses of Isolated Mouse Esophageal Striated Muscle to Carbachol The mechanisms which play role in the increase of carbachol induced responses of isolated mouse esophageal striated muscle by cadmium are investigated in this study. One third of upper and lower parts of isolated mouse esophagus were dissected out, mucosa was peeled off and preparations of 1 to 1.5 cm. were made ready. Tissue was mounted in organ bath under a tension of 250 mg. containing Krebs solution aerated with % 95 O2 and % 5 CO2 in 37 °C. After application of carbachol (2 x 10"4 M) which is a cholinomimetic drug, contractions with decreasing amplitudes were obtained. Following the first application of carbachol when Ca2+ channel antagonist cadmium (2x1 0"5 M) was added to the medium an increase was detected in the amplitudes of carbachol induced contractions. Another Ca2+ channel antagonist nickel (4x1 0"5 M) didn't change the carbachol induced contractions. A presynaptic nicotinic receptor antagonist hexamethonium (3x10^ M) decreased the carbachol induced contractions. Physostigmine (5xl07 M) which is an acetylcholinesterase inhibitor decreased the carbachol induced contractions in medium with cadmium. A postsynaptic nicotinic receptor blocker tubocurarine (10"7 M) decreased both carbachol induced contractions and carbachol induced contractions in medium with cadmium. But the responses in the mediums with tubocurarine and cadmium increased when compared to control contractions. Voltage sensitive calcium channel blockers verapamil (10"6, 10"5 M) and nifedipine (10"6, 10"s M) decreased both the carbachol control and cadmium control contractions in the concentration of 10"5 M. When calcium concentration is changed in 1.875 mM and 1.25 mM. carbachol contraction responses didn't change but in 1.25 mM contractions in medium with cadmium increased. In mediums without calcium and with EGTA (2xl0~3 and 10~2 M) carbachol contractions in both control and cadmium added mediums were inhibited. When calcium concentration is 5 mM and 7.5 mM the contractions decreased. Cyclopiazonic acid (10"5 M) which is a sarcoplasmic reticulum Ca+ ATPase enzyme inhibitor increased the carbachol contractions. Glutathion (10~3 M) and L cysteine (10"4 and 5x1ü"4 M) which are thiol modulators decreased the carbachol contractions in mediums with cadmium. Thiol oxidation agents ethacrinic acid (10"4 M) and diamid (10"5 M) increased the carbachol contractions. Trifluoperazine (10"5 M) which is a calmodulin e antagonist decreased the contraction responses. These results show that cadmium may increase the carbachol contractions by a myogenic effect or by interacting with intracellular and extracellular calcium concentration or by inhibition of sarcoplasmic reticulum calcium ATPase and increasing intracellular calcium concentration or by bounding to thiol groups or reduction the thiol reservoir and by functioning like calcium and binding to calmoduline. Key words: Esophagus, Carbachol, Cadmium, Striated muscle XVll