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Abstract

Activation of cyclic AMP-dependent protein kinase during canine lower esophageal sphincter relaxation.

M S Barnette, M Grous, T J Torphy and H S Ormsbee 3rd
Journal of Pharmacology and Experimental Therapeutics March 1990, 252 (3) 1160-1166;
M S Barnette
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M Grous
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T J Torphy
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H S Ormsbee 3rd
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Abstract

In isolated strips of opossum lower esophageal sphincter (LES) smooth muscle, elevation of cyclic AMP (cAMP) content is associated with relaxation. Because the activation state of cyclic nucleotide-dependent protein kinases may be a more sensitive measure of functionally important changes in cyclic nucleotide levels, we examined the ability of several pharmacological agents and electrical stimulation of the enteric neurons to activate cAMP dependent-protein kinase (cA-PK) and to relax isolated strips of LES smooth muscle. Addition of either isoproterenol or SK&F 94120, a selective inhibitor of the low Km cAMP phosphodiesterase to isolated strips of canine LES produced concentration-dependent increases in the activity ratio of cA-PK and concentration-dependent relaxations of canine LES. In contrast, although both zaprinast (M&B 22948), a selective inhibitor of the cyclic GMP selective phosphodiesterase, and sodium nitroprusside relaxed canine LES neither drug significantly increased the activity ratio of cA-PK. Furthermore, electrical stimulation of the enteric neurons produced a frequency-dependent relaxation but did not significantly activate cA-PK. To eliminate the possibility that the rapid metabolism of cAMP prevented us from observing a significant activation of cA-PK during electrical field stimulation, the ability of electrical field stimulation (1.0 Hz) to activate cA-PK was examined in the presence of 0.1 mM 3-isobutyl-1-methylxanthine. At at concentration of 0.1 mM, 3-isobutyl-1-methylxanthine, by itself, significantly increased the activity ratio of cA-PK; however, there was no additional activation produced by electrical field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 252, Issue 3
1 Mar 1990
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Abstract

Activation of cyclic AMP-dependent protein kinase during canine lower esophageal sphincter relaxation.

M S Barnette, M Grous, T J Torphy and H S Ormsbee
Journal of Pharmacology and Experimental Therapeutics March 1, 1990, 252 (3) 1160-1166;

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Abstract

Activation of cyclic AMP-dependent protein kinase during canine lower esophageal sphincter relaxation.

M S Barnette, M Grous, T J Torphy and H S Ormsbee
Journal of Pharmacology and Experimental Therapeutics March 1, 1990, 252 (3) 1160-1166;
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