Indomethacin, prostaglandin E2 and transmission at the frog neuromuscular junction.
The effects of indomethacin on transmission at the frog neuromuscular junction were studied using intra- and extracellular voltage recordings. The drug had two dose-dependent effects on spontaneous and evoked quantal acetylcholine release. Low doses (less than or equal to 30 microM) irreversibly decreased and high doses (greater than or equal to 300 microM) reversibly increased release. Indomethacin also increased the latencies of evoked responses by increasing synaptic delays and usually increasing nerve action potential conduction times. Low doses are thought to inhibit cyclo-oxygenase specifically. To determine whether this single action might account for the presynaptic effects of the drug, other treatments that affect prostaglandin concentrations were also studied: 1) potassium 5,8,11,14-eicosatetraynoate (3 microM) and phenylbutazone (80 micron or 1 mM), two additional, molecularly different synthesis inhibitors; 2) prostaglandin E2 (30 nM-30 microM); and 3) sodium arachidonate (30 nM-30 microM), the essential fatty acid precursor of prostaglandin E2. Each treatment altered transmission, but perturbations in endogenous prostaglandin concentrations cannot account for all of their presynaptic effects.
Madden
K S
KS
Van der Kloot
W
W
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D015232:Dinoprostone; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D009045:Motor Endplate / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D010653:Phenylbutazone / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis* / Q000494:pharmacology; D011894:Rana pipiens; D009435:Synaptic Transmission / Q000187:drug effects*
D001095:Arachidonic Acids; D011458:Prostaglandins E; D015117:5,8,11,14-Eicosatetraynoic Acid; C034152:11,14,17-eicosatrienoic acid; D016718:Arachidonic Acid; D015126:8,11,14-Eicosatrienoic Acid; D010653:Phenylbutazone; D015232:Dinoprostone; D000109:Acetylcholine; D007213:Indomethacin