Document Detail

Modulation of Ca2+ current in canine colonic myocytes by cyclic nucleotide-dependent mechanisms.
MedLine Citation:
PMID:  8843708     Owner:  NLM     Status:  MEDLINE    
Regulation of Ca2+ currents by cyclic nucleotide-dependent mechanisms was studied in circular muscle cells isolated from canine proximal colon. Whole cell Ca2+ currents were recorded at 32 degrees C with the use of amphotericin B-perforated patches. The effects of several agents known to increase levels of adenosine 3',5'-cyclic monophosphate (cAMP) were tested. Vasoactive intestinal peptide (VIP) and isoproterenol (10(-7) to 10(-5) M) increased Ca2+ current in a concentration-dependent manner. Forskolin (10(-7) M) and dibutyryl cAMP (10(-6) to 10(-5) M) also increased Ca2+ current. Higher concentrations of forskolin (10(-6) to 10(-5) M) caused inhibition of Ca2+ current. Low concentrations (10(-5) to 10(-7) M) of dibutyryl cAMP or 8-bromo-cAMP caused concentration-dependent enhancement in Ca2+ current, and these effects were reversible on washout of the cAMP analogues. When the concentration of cAMP analogues was increased (10(-3) to 10(-4) M), we observed inhibition of Ca2+ current similar to the effects of forskolin. Membrane-permeable analogues of guanosine 3',5'-cyclic monophosphate produced exclusively inhibitory effects. The nonspecific protein kinase inhibitor H-7 (up to 60 microM) failed to block the effects of VIP, isoproterenol, and forskolin, and it produced inhibitory effects on Ca2+ current, independent of agonist stimulation. The data suggest that low levels of cAMP may, via phosphorylation by protein kinase A, enhance L-type Ca2+ current, but higher concentrations of cAMP may "cross over" and activate protein kinase G. Phosphorylation by protein kinase G appears to produce a dominant inhibition of Ca2+ current.
S D Koh; K M Sanders
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  271     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1996 Sep 
Date Detail:
Created Date:  1996-12-05     Completed Date:  1996-12-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  C794-803     Citation Subset:  IM    
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno 89511, USA.
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MeSH Terms
Adrenergic alpha-Agonists / pharmacology
Bucladesine / pharmacology
Calcium / metabolism*
Cells, Cultured
Colon / metabolism*
Cyclic AMP / metabolism*
Forskolin / pharmacology
Ion Transport / drug effects
Isoproterenol / pharmacology
Muscle, Smooth / metabolism*
Patch-Clamp Techniques
Vasoactive Intestinal Peptide / pharmacology
Grant Support
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 362-74-3/Bucladesine; 37221-79-7/Vasoactive Intestinal Peptide; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 7440-70-2/Calcium; 7683-59-2/Isoproterenol

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