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Laminin binding to β1‐integrins selectively alters β1‐ and β2‐adrenoceptor signalling in cat atrial myocytes
- Source :
- The Journal of Physiology. 527:3-9
- Publication Year :
- 2000
- Publisher :
- Wiley, 2000.
-
Abstract
- 1. Perforated patch recordings were used to determine how plating atrial cells on laminin alters beta-adrenergic receptor (beta-AR) regulation of L-type Ca2+ current (ICa,L). 2. Isoproterenol (isoprenaline; ISO; 0.01 microM), a non-selective beta-AR agonist, elicited a greater stimulation of ICa,L in cells plated on laminin (+79 +/- 16 %; n = 17) than on glass (+33 +/- 5 %; n = 23). Also, desensitization to ISO was greater in cells on laminin (-16 +/- 2 %) than on glass (-3 +/- 1 %). Atenolol (0.1 microM), a selective beta1-AR antagonist, inhibited the effects of ISO in cells on glass but not laminin. Conversely, 0.1 microM ICI 118,551, a selective beta2-AR antagonist, inhibited the effects of ISO in cells on laminin but not glass. With beta2-ARs blocked, ISO-induced stimulation of ICa,L was greater in cells on glass than laminin. 3. Zinterol (0.01-0.1 microM), a selective beta2-AR agonist, elicited a greater stimulation of ICa,L in cells on laminin than on glass. The effects of zinterol were blocked by ICI 118,551. 4. ISO-induced stimulation of ICa,L was greater in cells plated on an alphabeta1-integrin antibody than on glass. Also, addition of 20 microM cytochalasin D to cells on laminin prevented the enhanced effects of ISO typically elicited in cells on laminin alone. 5. We conclude that laminin binding to alphabeta1-integrins, in conjunction with the actin cytoskeleton, reduces beta1-AR and enhances beta2-AR signalling which regulates ICa,L. This novel mechanism may contribute to remodelling of beta-AR signalling in the failing heart.
- Subjects :
- Male
Agonist
Calcium Channels, L-Type
Physiology
medicine.drug_class
Adrenergic beta-Antagonists
Down-Regulation
Stimulation
In Vitro Techniques
chemistry.chemical_compound
Adrenergic beta-2 Receptor Antagonists
Laminin
Isoprenaline
medicine
Animals
Heart Atria
Zinterol
Laminin binding
Adrenergic beta-2 Receptor Agonists
Cells, Cultured
Rapid Report
biology
Voltage-dependent calcium channel
Integrin beta1
Myocardium
Electric Conductivity
Isoproterenol
Adrenergic beta-Agonists
Actin cytoskeleton
Adrenergic beta-1 Receptor Antagonists
Molecular biology
Actins
Atenolol
chemistry
Immunology
Cats
biology.protein
Calcium
Female
Glass
Receptors, Adrenergic, beta-2
Receptors, Adrenergic, beta-1
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 14697793 and 00223751
- Volume :
- 527
- Database :
- OpenAIRE
- Journal :
- The Journal of Physiology
- Accession number :
- edsair.doi.dedup.....2709e6b7dd4b45d39a5b50c8d789ceb0