Document Detail

Cyclic AMP dependent down regulation in the relaxation of smooth muscle cells of cat esophagitis.
MedLine Citation:
PMID:  17679549     Owner:  NLM     Status:  MEDLINE    
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 HCI 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-con tracted 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 ana log) also induced dose-dependent relaxation to a similar extent in both normal and esoph agitic cells. Forskolin (a cAMP activator) or db-cAMP (a cAMP analog) produced dose-dependent relaxation in normal cells, and this relaxation curve was down shifted in esoph agitic 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 activ ity of adenylyl cyclase V/VI.
Chang Yell Shin; Yul Pyo Lee; Hyun Ju Song; Hyun Dong Je; Uy Dong Sohn
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Archives of pharmacal research     Volume:  30     ISSN:  0253-6269     ISO Abbreviation:  Arch. Pharm. Res.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-08-07     Completed Date:  2007-10-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000036     Medline TA:  Arch Pharm Res     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  715-22     Citation Subset:  IM    
Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.
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MeSH Terms
Adenylate Cyclase / metabolism
Blotting, Western
Bucladesine / pharmacology
Cell Membrane Permeability / physiology
Cyclic AMP / biosynthesis,  physiology*
Cyclic GMP / physiology
Dose-Response Relationship, Drug
Down-Regulation / physiology
Esophagitis / physiopathology*
Forskolin / pharmacology
Isoenzymes / metabolism
Molsidomine / analogs & derivatives,  pharmacology
Muscle Relaxation / physiology
Muscle, Smooth / physiology*
Nitric Oxide Donors / pharmacology
Nitroprusside / pharmacology
Signal Transduction / physiology
Vasoactive Intestinal Peptide / pharmacology
Reg. No./Substance:
0/Isoenzymes; 0/Nitric Oxide Donors; 15078-28-1/Nitroprusside; 25717-80-0/Molsidomine; 33876-97-0/3-morpholino-sydnonimine; 362-74-3/Bucladesine; 37221-79-7/Vasoactive Intestinal Peptide; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 7665-99-8/Cyclic GMP; EC Cyclase

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