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1 Dept. of Cardiology, Sant'Andrea Hospital, Rome, Italy
2 Dept. of Pharmacology, University of Rome "La Sapienza", II School of Medicine, Rome, Italy
3 Dept. of Histology, University of Rome "La Sapienza", I School of Medicine, Rome, Italy
4 Dept. of Pathology, Catholic University, Rome, Italy
5 Dept. of Pharmacy, University of Chieti, Chieti, Italy
6 Dept. of Biomedical Sciences, University of Padua, Padua, Italy
7 Dept. of Cardiology, Sant'Andrea Hospital, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy
8 Dept. of Human Anatomy and Physiology, University of Padua, Padua, Italy
* To whom correspondence should be addressed. E-mail: mar.testa{at}tin.it.
Conflicting data have been reported on cyclooxygenase (COX)-1 and COX-2 expression and activity in striated muscles, including skeletal muscles and myocardium, in particular it is still unclear whether muscle cells are able to produce prostaglandins. We characterized the expression and enzymatic activity of COX-1 and COX-2 in the skeletal muscles and in the myocardium of mice, rats and humans. By RT-PCR, COX-1 and COX-2 mRNAs were observed in homogenates of mouse and rat hearts, and in different types of skeletal muscles from all different species. By Western blottings, COX-1 and -2 proteins were detected in skeletal muscles and hearts from rodents, as well as in skeletal muscle from humans. Immunoperoxidase stains showed that COX-1 and -2 were diffusely expressed in the myocytes of different muscles and in the myocardiocytes from all different species. In the presence of arachidonic acid, which is the COX enzymatic substrate, isolated skeletal muscle and heart samples from rodents released predominantly prostaglandin (PG) E2. The biosynthesis of PGE2 was reduced between 50 and 80% (p<0.05 vs. vehicle) in the presence of either COX-1- or COX-2-selective blockers, demonstrating that both isoforms are enzymatically active. Exogenous PGE2 added to isolated skeletal muscle preparations from rodents did not affect contraction, while it significantly fastened relaxation of a slow type of muscle, such as soleus. In conclusion, COX-1 and COX-2 are expressed and enzymatically active in myocytes of skeletal muscles and hearts of rodents and humans. PGE2 appears to be the main product of cyclooxygenase activity in striated muscles.
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