QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Barry, S. R. Search for Related Content PubMed PubMed Citation Articles by Barry, S. R.

 Previous Article  |  Next Article 

Journal of Neuroscience, Vol 8, 4427-4433, Copyright © 1988 by Society for Neuroscience

ARTICLE

Dual effects of theophylline on spontaneous transmitter release from frog motor nerve terminals

SR Barry
Department of Physical Medicine and Rehabilitation, University Hospital, University of Michigan, Ann Arbor 48109-0042.

Alkylxanthine drugs, such as theophylline, block adenosine receptors, inhibit phosphodiesterases and other enzymes, and cause the release of calcium from intracellular stores. Adenosine receptor blockade occurs at low micromolar concentrations of the drugs, while other effects occur in the millimolar concentration range. The effects of theophylline were tested on spontaneous transmitter release at the frog cutaneous-pectoris neuromuscular junction (NMJ). A change in the frequency, but not the amplitude, of miniature endplate potentials (mepps) was interpreted as a change in spontaneous transmitter release. In normal Ringer's, theophylline, at concentrations of 100 microM and 1 mM, theophylline had no consistent effect on spontaneous release. In contrast, theophylline produced dual effects on mepp frequency in hyperosmotic Ringer's. At 10 microM, theophylline depressed mepp frequency, while, at 100 microM and 1 mM, theophylline increased mepp rate. Since low micromolar concentrations of theophylline depressed spontaneous transmitter release, this action may result from adenosine receptor blockade and inhibition of a tonic, stimulatory effect of adenosine. This hypothesis was supported by the following experimental results: (1) Micromolar concentrations of theophylline reversed the effects of applied adenosine on neuromuscular transmission. (2) The inhibitory effect of theophylline was mimicked by 2 other alkylxanthines, 8-phenyltheophylline and 8-p-sulfophenyltheophylline. These drugs may be more specific adenosine receptor antagonists than theophylline. (3) The inhibitory effect of theophylline was mimicked by adenosine deaminase, an enzyme that breaks down and inactivates adenosine. (4) The depressant action of theophylline was masked by the addition of adenosine deaminase to the hyperosmotic Ringer's. Application of adenosine to the frog NMJ reduces spontaneous transmitter output.(ABSTRACT TRUNCATED AT 250 WORDS)

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help