Abstract |
Decreased beta-adrenergic receptor (beta-AR) number occurs both in animal models of cardiac hypertrophy and failure and in patients. beta-AR recycling is an important mechanism for the beta-AR resensitization that maintains a normal complement of cell surface beta-ARs. We have shown that 1) in severe pressure overload cardiac hypertrophy, there is extensive microtubule-associated protein 4 ( MAP4) decoration of a dense microtubule network; and 2) MAP4 microtubule decoration inhibits muscarinic acetylcholine receptor recycling in neuroblastoma cells. We asked here whether MAP4 microtubule decoration inhibits beta-AR recycling in adult cardiocytes. [(3)H] CGP-12177 was used as a beta-AR ligand, and feline cardiocytes were isolated and infected with adenovirus containing MAP4 (AdMAP4) or beta-galactosidase (Adbeta-gal) cDNA. MAP4 decorated the microtubules extensively only in AdMAP4 cardiocytes. beta-AR agonist exposure reduced cell surface beta-AR number comparably in AdMAP4 and Adbeta-gal cardiocytes; however, after agonist withdrawal, the cell surface beta-AR number recovered to 78.4 +/- 2.9% of the pretreatment value in Adbeta-gal cardiocytes but only to 56.8 +/- 1.4% in AdMAP4 cardiocytes (P < 0.01). This result was confirmed in cardiocytes isolated from transgenic mice having cardiac-restricted MAP4 overexpression. In functional terms of cAMP generation, beta-AR agonist responsiveness of AdMAP4 cells was 47% less than that of Adbeta-gal cells. We conclude that MAP4 microtubule decoration interferes with beta-AR recycling and that this may be one mechanism for beta-AR downregulation in heart failure.
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Authors | Guangmao Cheng, Fei Qiao, Thomas N Gallien, Dhandapani Kuppuswamy, George Cooper 4th |
Journal | American journal of physiology. Heart and circulatory physiology
(Am J Physiol Heart Circ Physiol)
Vol. 288
Issue 3
Pg. H1193-202
(Mar 2005)
ISSN: 0363-6135 [Print] United States |
PMID | 15528234
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Adrenergic beta-Agonists
- Microtubule-Associated Proteins
- Propanolamines
- Receptors, Adrenergic, beta
- Tritium
- Cyclic AMP
- CGP 12177
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Topics |
- Adenoviridae
(genetics)
- Adrenergic beta-Agonists
(metabolism, pharmacology)
- Animals
- Cats
- Cells, Cultured
- Cyclic AMP
(metabolism)
- Down-Regulation
(physiology)
- Female
- Gene Expression
- Gene Transfer Techniques
- Heart Ventricles
(cytology, metabolism)
- Humans
- Male
- Mice
- Microtubule-Associated Proteins
(genetics, metabolism)
- Microtubules
(metabolism)
- Myocardium
(cytology, metabolism)
- Myocytes, Cardiac
(cytology, metabolism)
- Propanolamines
(metabolism, pharmacology)
- Receptors, Adrenergic, beta
(metabolism)
- Tritium
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