Different spasmolytic effects of smooth muscle relaxants on the guinea-pig esophageal muscularis mucosae contracted by carbachol or high potassium in vitro.

ABSTRACT

The responsiveness of the guinea-pig esophageal muscularis mucosae to smooth muscle relaxants was examined in vitro during the contractile state induced by carbachol (3 microM) or high potassium (60 mM). In the presence of phentolamine (3 microM), all catecholamines tested (10 nM-30 microM) relaxed the carbachol-induced tone more effectively than the high potassium-induced tone, and the maximum relaxations reached about 90-95% for carbachol but only about 40% for high potassium. Verapamil produced a concentration-dependent relaxation of the muscularis mucosae precontracted with either spasmogen; the mean EC50 values (-log M) were 6.73 for high potassium and 4.65 for carbachol. Methylene blue (1-300 microM) relaxed the carbachol-contracted muscularis mucosae in a concentration-dependent manner but relaxed the high potassium-contracted one less potently. Forskolin (1-300 microM), papaverine (1-100 microM), aminophylline (10-300 microM), trifluoperazine (1-300 microM), 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (10-300 microM), quinacrine (1-300 microM) and dibutyryl cyclic AMP (100 microM-3 mM) produced relaxation almost equipotently in both contractile states whereas adenosine (10 microM-1 mM), sodium nitroprusside (10-300 microM) and dibutyryl cyclic GMP (100 microM-3 mM) were virtually ineffective. The present results indicate that a variety of smooth muscle relaxants have different spasmolytic effects on the guinea-pig isolated esophageal muscularis mucosae which was precontracted with carbachol or high potassium and that catecholamines and methylene blue may produce relaxation independent of the changes in intracellular cyclic nucleotides, calmodulin or phosphoinositides.