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Received May 23, 2002
Accepted after revision July 11, 2002
1 Department of Physiology, National Institute of Occupational Health, PO Box 8149 Dep, N-0033 Oslo, Norway
2 Department of Physiology, National Institute of Occupational Health, Oslo, Norway
3 Department of Pharmaceutical Pharmacology, University of Heidelberg, Heidelberg, Germany,
4 Department of Physiology, National Institute of Occupational Health, Oslo, Norway and Department of Psychology, University of Oslo, Oslo, Norway
* To whom correspondence should be addressed. E-mail: Fernando.Boix{at}stami.no.
In order to study the effects of the manipulation of various factors related to muscular activity on the concentration of kinins in muscular tissue, a microdialysis probe was implanted in the adductor muscle of the hindlimb in anesthetized rats. After collection of baseline samples, the perfusion fluid was changed to a Ringer solution containing sodium lactate (10 or 20 mM), adenosine (50 or 100 µM) or a lower pH (7.0 or 6.6). Whereas perfusion with lactate did not have any significant effect on the concentration of kinins in the dialysate, the perfusion with a lower pH or with adenosine dose-dependently increased the kinin content in the samples. In a second microdialysis experiment, by using specific radioimmunoassays (RIA) for bradykinin and kallidin, we observed that about 70 % of the total kinins dialysed from rat muscle are a kallidin-like peptide. Also, the simultaneous perfusion with 100 µM caffeine totally abolished the increase in kinin levels induced by the perfusion at pH 6.6. In a third experiment, soleus muscles from rat were stimulated in vitro during 30 min in the presence or absence of 77 µM caffeine. Electrically stimulated contraction, but not the addition of 10 mU ml-1 insulin, induced an increase in the concentration of the kallidin-like peptide in the buffer. This effect was totally prevented by the addition of the adenosine antagonist caffeine. These results show that a kallidin-like peptide is released from rat muscle, and that its production is enhanced by muscle activity. Furthermore, the increase in kinin peptides during muscle contraction may be mediated by an increase in adenosine levels.
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