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Application of Chronic Stimulation to Study Contractile Activity-induced Rat Skeletal Muscle Phenotypic Adaptations
Published on: January 25, 2018
Skeletal muscle expresses the extracellular cyclic AMP-adenosine pathway
T Chiavegatti1, V L Costa, M S Araújo
1Department of Pharmacology, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Três de Maio, São Paulo, SP, Brazil.
British Journal of Pharmacology
|December 25, 2007
Summary
Skeletal muscle cells actively release cyclic adenosine monophosphate (cAMP). This extracellular cAMP is converted to adenosine, creating a paracrine signaling pathway that amplifies cellular responses.
Area of Science:
- Biochemistry
- Cell Biology
- Physiology
Background:
- Cyclic adenosine monophosphate (cAMP) is a crucial intracellular signaling molecule in vertebrate skeletal muscle.
- Previous research indicates cAMP can be actively transported out of skeletal muscle cells.
- Extracellular cAMP generation has been linked to adenosine production in other tissues.
Purpose of the Study:
- To investigate the fate of interstitial cAMP in skeletal muscle.
- To determine the existence of an extracellular cAMP-adenosine signaling pathway in skeletal muscle.
Main Methods:
- Rat cultured skeletal muscle cells were incubated with exogenous cAMP, forskolin, or isoprenaline.
- cAMP efflux and extracellular degradation were analyzed.
- cAMP and its metabolites (5'-AMP, adenosine) were quantified using radioassay or HPLC.
Main Results:
- Exogenous cAMP incubation led to interstitial accumulation of 5'-AMP and adenosine, inhibited by ecto-phosphodiesterase and ecto-nucleotidase inhibitors.
- Activation of adenylyl cyclase (AC) increased cAMP efflux and extracellular 5'-AMP and adenosine generation.
- This extracellular pathway was confirmed ex vivo and attenuated by probenecid, an inhibitor of ATP binding cassette transporters.
Conclusions:
- An extracellular biochemical cascade converting cAMP to adenosine exists in skeletal muscle.
- This pathway amplifies cAMP's influence via adenosine, potentially modulating cellular responses in a paracrine manner.
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