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KMID : 0043320070300060715
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Archives of Pharmacal Research
2007 Volume.30 No. 6 p.715 ~ p.722
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Cyclic AMP Dependent Down Regulation in the Relaxation of Smooth Muscle Cells of Cat Esophagitis
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Shin Chang-Yell
Lee Yul-Pyo
Song Hyun-Ju
Je Hyun-Dong
Sohn Uy-Dong
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Abstract
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We investigated whether the signal mechanism for relaxation may be affected by inflammation of the cat esophagus. Acute esophagitis was induced by perfusion with 0.1N HCl at a rate of 1 mL/min for 45 min over three consecutive days. We then isolated esophageal smooth muscle cells by enzymatic digestion with collagenase. We pre-contracted the isolated smooth cells with acetylcholine (ACh) (10-5 M) and compared the agonist-induced relaxation of pre-contracted normal cells with those of esophagitic cells. Vasoactive intestinal polypeptide (VIP) caused a dose-dependent relaxation in normal cells, and this curve was down shifted in esophagitic cells. Sodium nitroprusside (SNP) or SIN-1 (NO donor) produced dose-dependent relaxation in normal cells, which was not affected by esophagitis. 8-Br-cGMP (a cGMP analog) also induced dose-dependent relaxation to a similar extent in both normal and esophagitic cells. Forskolin (a cAMP activator) or db-cAMP (a cAMP analog) produced dosedependent relaxation in normal cells, and this relaxation curve was down shifted in esophagitic cells. Western blotting was used to determine what subtype of adenylyl cyclase was involved in the cAMP pathway. Western blot analysis of homogenates derived from esophageal smooth muscle using antibodies against adenylyl cyclase types II, III, IV and V/VI revealed the presence of type V and/or type VI only. This result suggests that relaxation via a cAMP-dependent pathway rather than a cGMP dependent-pathway is down regulated in cat acute esophagitis. This subsensitivity of the cAMP related pathway may be related to the activity of adenylyl cyclase V/VI.
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KEYWORD
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Esophagitis, VIP, Relaxation, cAMP, Adenylyl cyclase
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